2024-03-28T09:43:11Zhttps://kuscholarworks.ku.edu/oai/requestoai:kuscholarworks.ku.edu:1808/62792020-07-29T12:07:23Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Munson, Eric J.
author
Schieber, Loren J.
cmtemember
Berkland, Cory J.
cmtemember
Gehrke, Stevin H.
cmtemember
Lunte, Susan M.
cmtemember
Stobaugh, John F.
2010-06-09T02:47:01Z
2010-06-09T02:47:01Z
2010-01-22
http://dissertations.umi.com/ku:10723
http://hdl.handle.net/1808/6279
Solid-state nuclear magnetic resonance (SSNMR) spectroscopy has been demonstrated to be a powerful technique for investigating solid dosage formulations. SSNMR has the ability to determine physical form, molecular structure, and dynamics of a pure or formulated active pharmaceutical ingredient (API). To overcome the major shortcomings of SSNMR, acquisition time and sensitivity, a two-sample probe was designed, developed, and tested. The probe allowed for two samples to be acquired simultaneously while being shuttled through the magnet bore with a stepper motor, and exhibited signal to noise ratio (SNR) values comparable to current probes. Pharmaceutical relevance was demonstrated by acquiring spectra of ibuprofen and aspirin simultaneously. 19F SSNMR was used to examine low-level amorphous impurities in crystalline physical mixtures. The model compound was chosen for amorphous form stability, cost, and 19F SSNMR spectral resolution between the crystalline and amorphous solid forms. Triamcinolone was selected for quantitation studies using 19F SSNMR.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Amorphous
Fluorine
Nmr
Oxygen
Relaxation
Solid-state
Methods for Increasing Sensitivity and Throughput of Solid-State NMR Spectroscopy of Pharmaceutical Solids
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6279/1/Schieber_ku_0099D_10723_DATA_1.pdf
File
MD5
dbe886412d930e87271988c31920bf01
8901591
application/pdf
Schieber_ku_0099D_10723_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6279/2/Schieber_ku_0099D_10723_DATA_1.pdf.txt
File
MD5
f5482fa8489a693fd7c02cc5cb1acbca
283301
text/plain
Schieber_ku_0099D_10723_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216442018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Krise, Jeffrey
author
Ormes, James Daniel
cmtemember
Marsac, Patrick J
cmtemember
Forrest, Laird
2016-10-11T16:56:39Z
2016-10-11T16:56:39Z
2014-08-31
http://dissertations.umi.com/ku:13503
http://hdl.handle.net/1808/21644
Suspensions of spray dried amorphous dispersions are a valuable tool for enhancing the exposure of poorly soluble compounds in preclinical animal models. However, limitations in drug supply and time/cost of manufacture in the drug discovery space make it desirable to predict the likelihood of obtaining a physically stable (free from detectable crystallization) suspension prior to synthetic scale-up and processing of a candidate compound. Background information on this topic is covered in Chapter 1. For 33.3% drug load solid dispersions in Hydroxypropylmethyl cellulose acetate succinate (HPMCAS) suspended in 0.5% Methocel + 0.25% sodium lauryl sulfate (SLS) + 5 mM HCl, a platform formulation frequently used in discovery, a 2-tiered model can be used to correctly predict the stability of 22 of 24 model compounds. First, the model considers the humidity adjusted glass transition temperature of the solid dispersion (Tg,dispersion,100% RH). For compounds where Tg,dispersion,100% RH is >30 °C, the dispersion is typically free from crystallization within 3 hours of preparation, which is attributed to a decrease in molecular mobility. 3 hours was selected as the timeframe between suspension preparation and dosing for the purpose of the present research. For compounds where Tg,dispersion,100% RH is 30 °C, the dispersion is typically free from crystallization within 3 hours of preparation, which is attributed to a decrease in molecular mobility. 3 hours was selected as the timeframe between suspension preparation and dosing for the purpose of the present research. For compounds where Tg,dispersion,100% RH is 1000 to be predicted stable) can be used to successfully predict a 3 hour shelf-life.
en
Copyright held by the author.
Pharmaceutical sciences
Amorphous
Crystallization
Dispersions
Glass
HPMCAS
Suspensions
Predicting the Risk of Crystallization for Suspensions of Amorphous Spray Dried Dispersions from Structural, Thermal and Hydrophilicity Properties
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21644/1/Ormes_ku_0099M_13503_DATA_1.pdf
File
MD5
3b17c10300bb37c4479931bb1cb8a1ec
11433374
application/pdf
Ormes_ku_0099M_13503_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21644/2/Ormes_ku_0099M_13503_DATA_1.pdf.txt
File
MD5
22719b86fdaa8bc91858f5fa2bdf17af
147821
text/plain
Ormes_ku_0099M_13503_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/298412021-03-05T19:02:11Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory
author
Christopher, Matthew Alexander
cmtemember
Siahaan, Teruna
cmtemember
Volkin, David
cmtemember
Forrest, Laird
cmtemember
Paul, Arghya
2019-12-10T20:38:47Z
2019-12-10T20:38:47Z
2019-08-31
http://dissertations.umi.com/ku:16757
http://hdl.handle.net/1808/29841
https://orcid.org/0000-0002-5008-8771
Current therapies for autoimmune diseases lack specificity for the offending immune cell population resulting in a wide range of side effects and weakening of the immune system. This presents a clear need for antigen-specific immunotherapies (ASITs) capable of selectively modulating autoreactive immune cells while maintaining the patient’s ability to respond to foreign pathogens. Lymphocyte activation is dependent on receiving two signals in tandem: interaction with the antigen of interest and co-stimulatory signals. Disruption of this two-signal model for lymphocyte activation in the context of the autoantigen is key to developing successful ASITs. Antigen-drug conjugates represent a novel class of therapeutics for the induction of immune tolerance designed to direct the effects of small molecule immunosuppressants through conjugation to the autoantigen of interest (Chapter 2). This strategy has proven successful in ameliorating paralytic symptoms in a murine model of multiple sclerosis (MS) known as experimental autoimmune encephalomyelitis (EAE). This was achieved through conjugation of the corticosteroid dexamethasone (DEX) to the peptide autoantigen proteolipid protein (PLP139-151). Further studies into the disruption of co-stimulatory signals in EAE revealed a protective role for the programmed cell death 1 (PD-1) pathway, and antagonism of natural receptor engagement resulted in cellular exhaustion, alleviating inflammatory markers (Chapter 3). Ultimately, antigen-only ASITs represent possibly the safest form of immune modulation in autoimmune diseases and may be achieved through multivalent displays of autoantigen. For example, a tetravalent display of PLP139-151 (4-arm PLP139-151) completely ameliorated EAE symptoms through depletion of PLP-responsive B cells and induction of a tolerogenic shift in co-stimulatory markers (Chapter 4). These results support the advancement of multiple avenues of approach in the development of ASIT for treating autoimmunity.
en
Copyright held by the author.
Pharmaceutical sciences
Immunology
Antigen-Specific Immunotherapy
Autoimmunity
Experimental Autoimmune Encephalomyelitis
Immunotherapy
Design of Antigen-Specific Immunotherapies Through Modulation of Peripheral Tolerance Pathways
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29841/1/Christopher_ku_0099D_16757_DATA_1.pdf
File
MD5
66d98f8d3cfc1cc080047fa3ad33c5c2
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Christopher_ku_0099D_16757_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29841/2/Christopher_ku_0099D_16757_DATA_1.pdf.txt
File
MD5
f9b90d4f3305b0410db359a664658210
177594
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Christopher_ku_0099D_16757_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253882018-09-20T19:46:04Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory J
author
Pickens, Chad James
cmtemember
Middaugh, Russell
cmtemember
Picking, William
cmtemember
Tolbert, Thomas
cmtemember
Prisinzano, Thomas
2017-11-16T04:11:27Z
2017-11-16T04:11:27Z
2017-08-31
http://dissertations.umi.com/ku:15529
http://hdl.handle.net/1808/25388
Autoimmune disorders are a challenging problem for both afflicted patients and pharmaceutical scientists, since they involve one of the most complex biological systems – the immune system. A dysregulation of antigen recognition is at the center of autoimmune disorders, and can occur in a variety of host tissues throughout the body. Further complicating these diseases is the high degree of variability in terms of clinical manifestation. Traditional therapies for autoimmune disorders, such as corticosteroids or immunomodulators, generally focus on symptom suppression or slowing disease progression rather than treating the underlying cause, which is rarely fully understood. New approaches to treatments in which a disease-causing autoantigen is known seek to leverage antigen specificity through the development of antigen-specific immunotherapies (ASIT). In this research, we explore different novel approaches to ASIT focused on chemical conjugation, including the design and development of a new therapeutic class, antigen-drug conjugates (AgDCs). By reversing the paradigm of antibody-drug conjugates (ADCs), AgDCs exploit the directing effect of the autoantigen towards diseased cell populations, coupled with the immunomodulatory effects of a small molecule drug. Soluble Antigen Arrays (SAgAs) focus on disrupting immune recognition at the immunological synapse by conjugating autoantigen on a multivalent polymer support. Polymer-drug conjugates also present a unique opportunity as a depot delivery system with the potential for targeted applications. The strategies presented here carry an overarching goal to increase therapeutic specificity while limiting off-target effects, in an attempt to develop improved treatments with better efficacy and safety profiles for patients.
en
Copyright held by the author.
Pharmaceutical sciences
Immunology
Antigen
Conjugate
Immunotherapy
Multivalent
Specific
Targeted
Design of Novel Antigen-Specific Immunotherapies for the Treatment of Autoimmune Disorders
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25388/1/Pickens_ku_0099D_15529_DATA_1.pdf
File
MD5
62a38be9969e41bb1d191f08e981ac24
5037500
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Pickens_ku_0099D_15529_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25388/2/Pickens_ku_0099D_15529_DATA_1.pdf.txt
File
MD5
82451fd5b9fcd3bab6cce09b92aee44b
243054
text/plain
Pickens_ku_0099D_15529_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/61852020-06-18T01:23:27Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Audus, Kenneth L
author
Mitra, Pallabi
cmtemember
Krise, Jeffrey P.
cmtemember
Lunte, Susan M.
cmtemember
Siahaan, Teruna J.
cmtemember
Soares, Michael J
2010-05-03T01:10:18Z
2010-05-03T01:10:18Z
2009-01-28
http://dissertations.umi.com/ku:10193
http://hdl.handle.net/1808/6185
The trophoblast cell layer constitutes the rate-determining barrier for trans-placental transfer. Several isoforms of the sulfotransferase enzymes are functional in placenta but there is only limited information available on the utility of cultured trophoblast cells for studying placental sulfation. We examined the expression and activities of four sulfotransferase isoforms (SULT1A1, SULT1A3, SULT1E1, and SULT2A1) in primary cytotrophoblast cells and the trophoblast-like BeWo cell line. These isoforms have been reported to be functional in human placenta. Our results indicated that the phenolic sulfotransferase isoforms, SULT1A1 and SULT1A3, are functional in BeWo, as well as in the primary cytotrophoblast cells. SULT2A1 and SULT1E1 are not functional in either cell type. We also found that chronic exposure to the industrial chemical bisphenol A inhibited SULT1A1 activity. A U-shaped dose-response curve was observed with inhibition (~30-40%) being observed only at intermediate concentrations (10-100 nM). These results suggested that trophoblast cells may be used as a suitable in vitro tool to determine the effect of endogenous or exogenous substances on placental sulfotransferase activity. Altered metabolic activity has the chance of altering fetal exposure to drugs and other substances in the maternal circulation. Studies performed in BeWo cells also suggested that one of the roles of the placental efflux transporters is the elimination of sulfate metabolites. The multidrug resistance-associated proteins (MRPs) played a major role in the elimination of 4-nitrophenyl sulfate and acetaminophen sulfate across the basolateral (fetal-facing) and apical (maternal-facing) trophoblast membranes respectively. The breast cancer resistance protein (BCRP) played a minor role in the elimination of these two sulfate conjugates across the apical membrane.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Bisphenol a
Breast cancer resistance protein (bcrp)
Multidrug resistance-associated protein (mrp)
Placenta
Sulfotransferase enzymes
Trophoblast
ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6185/1/Mitra_ku_0099D_10193_DATA_1.pdf
File
MD5
fb278dc494d28ea483fdda445bd36f99
3813617
application/pdf
Mitra_ku_0099D_10193_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6185/2/Mitra_ku_0099D_10193_DATA_1.pdf.txt
File
MD5
3012138b8724fb7fe3ebc05e0fe0151b
264356
text/plain
Mitra_ku_0099D_10193_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/121882020-10-07T13:31:25Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Wang, Michael Z
author
Michaels, Scott
cmtemember
Wolfe, Janet L
cmtemember
Lunte, Susan M.
2013-09-29T14:11:44Z
2013-09-29T14:11:44Z
2013-08-31
http://dissertations.umi.com/ku:12903
http://hdl.handle.net/1808/12188
The purpose of the work presented herein was to determine the absolute protein content of multiple cytochrome P450 (CYP) enzymes in individual donor human liver microsome (HLM) samples. The CYP4F subfamily of enzymes have recently been identified to be involved in the metabolism of endogenous compounds (arachidonic acid, leukotriene B4), nutrients (vitamin K1 and vitamin E), and xenobiotics (parfuramidine (DB289), DB1230, fingolimod). The CYP3A subfamily of enzymes are known to metabolize a wide variety of physiologically and pharmaceutically important substances. The determination of the absolute enzyme protein content and the inter-individual variability in the expression of these enzymes is important in understanding the effects they may have on the disposition of both endogenous and exogenous substances. Therefore, the absolute enzyme protein content in 20 individual donor HLM was determined by LC/MS/MS for CYP4F2, CYP4F3B, CYP3A, CYP3A4, and CYP3A5. The contribution of CYP4F enzymes to the overall hepatic CYP "pie" was also determined. The observed enzyme protein values were then correlated with immunoquantified protein content and enzyme activity. The enzyme protein contents determined by LC/MS/MS were well correlated with immunoquantification results (r2 ≥ 0.60) for both CYP4F and CYP3A. The CYP4F enzymes displayed significantly less (~2- to 4-fold) variability than did the CYP3A enzymes (~7- to 20-fold). The CYP4F protein contents did not correlate with primary metabolite formation rates for DB289 or DB1230. Chemical inhibition experiments were performed which provided additional evidence for the metabolism for DB289 and DB1230 by enzymes other than CYP4F enzymes. However, a lack of improved correlation for the chemical inhibition experiments suggest that the poor correlation observed for CYP4F protein content and metabolic activity is not solely due to the contributions of additional enzymes. The LC/MS/MS methodology used for the current study has thus been shown to provide a rapid and reproducible (CV ≤ 24%) method for quantitation of enzyme protein expression level that obviates the need for specific antibodies for immunoquantification, a major problem for the less commonly studied enzymes that share significant sequence homology such as the CYP4F enzymes.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Acitivity
Cyp4f
Enzyme
Immunoquantification
Lc/ms/ms
Proteomics
Determination of Absolute Protein Content of Hepatic CYP4F Enzymes in Human Liver Microsomes Using LC/MS/MS Methodology and Comparison with Immunoquantification and Enzyme Activity
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/12188/1/Michaels_ku_0099M_12903_DATA_1.pdf
File
MD5
1d76d51e9093c3838f08b33e34126b2c
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application/pdf
Michaels_ku_0099M_12903_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/12188/2/Michaels_ku_0099M_12903_DATA_1.pdf.txt
File
MD5
a16d0256581b02bddf58f596722f1dd0
85650
text/plain
Michaels_ku_0099M_12903_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/298472021-03-05T16:53:01Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Laird
author
Moulder, Kenneth Ryan
cmtemember
Berkland, Cory
cmtemember
Middaugh, Russell
cmtemember
Siahaan, Teruna
cmtemember
Paul, Arghya
2019-12-10T20:52:27Z
2019-12-10T20:52:27Z
2019-08-31
http://dissertations.umi.com/ku:16765
http://hdl.handle.net/1808/29847
The inherent properties of protein therapeutics (e.g. high molecular weight, charged, conformationally dependent) has historically limited their administration to parenteral routes which presents new challenges to their controlled delivery. Hydrogel and nanoparticle drug delivery systems can parenterally deliver a wide variety of drugs in a controlled manner while sustaining their therapeutic efficacy. Nanogels, formed from amphiphilic polymers, combine the unique and tunable properties of hydrogels and nanoparticles into one drug delivery system and have the potential to drastically improve the clinical applicability of protein therapeutics delivered subcutaneously. Hyaluronic acid, a ubiquitous polysaccharide of the extracellular matrix often used in drug delivery applications, was hydrophobically functionalized by the addition of glycine-modified vitamin E (-tocopherol) to form a self-assembling nanogel (HAtoco). The characterization of HAtoco was further developed by modifying its molecular weight and tocopherol substitution towards an optimum 33 kDa backbone with a 10mol% substitution. Physical and chemical characterization of the optimum HAtoco demonstrated its polydisperse effective size, stable colloidal and chemical stability and continued biodegradability by the endogenous enzyme hyaluronidase. In addition, HAtoco has shown the ability to double the in vitro release half-life of three model proteins (BSA, RNase, Lysozyme) and the in vivo release half-life of the clinical protein therapeutic Coversin when delivered subcutaneously to mice. Structural studies of HAtoco bound Coversin demonstrated destabilization of the protein upon adsorption, but released Coversin from the HAtoco nanogel demonstrated complement inhibition for at least 73 hours in vitro. Overall, HAtoco has demonstrated the ability to bind protein therapeutics in a reversible manner capable of prolonging their release in a therapeutically efficacious state.
en
Copyright held by the author.
Pharmaceutical sciences
Coversin
Hyaluronic acid
Nanogel
Vitamin E
Development and biophysical characterization of a hyaluronic acid – vitamin E conjugate as a subcutaneous delivery platform
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29847/1/Moulder_ku_0099D_16765_DATA_1.pdf
File
MD5
633b79ce5de2ba26398a4ba905e88e70
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Moulder_ku_0099D_16765_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29847/2/Moulder_ku_0099D_16765_DATA_1.pdf.txt
File
MD5
12937cb90891ae0f5b47ed33850edd02
244184
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Moulder_ku_0099D_16765_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/278532019-08-27T18:09:08Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, Russell C
author
Angalakurthi, Siva krishna
cmtemember
Picking, William
cmtemember
Siahaan, Teruna J
cmtemember
Tolbert, Thomas
cmtemember
Dhar, Prajnaparamita
2019-05-10T17:02:47Z
2019-05-10T17:02:47Z
2018-12-31
http://dissertations.umi.com/ku:16258
http://hdl.handle.net/1808/27853
Ricin toxin’s enzymatic A subunit (RTA) is a 267 amino acid RNA N-glycosidase that depurinates a conserved adenine residue of 28S rRNA, resulting in ribosome arrest and apoptosis. One of the leading subunit vaccine candidates for ricin is RiVax, a two point mutant (V76M, Y80A) of RTA. RiVax has proven to be safe in humans, however, it could not elicit a robust toxin-neutralizing antibody response. In order to redesign a potent ricin subunit vaccine candidate based on RTA, an immunological rationale has to be implemented. Protection against ricin is antibody mediated and hence generating a comprehensive B cell epitope map of ricin toxin would not only help in evaluating future ricin vaccine candidates in humans but also provides an immunological rationale for designing new vaccine candidates. Previous studies have shown that toxin neutralizing antibodies recognized four immunodominant regions on RTA i.e. four epitope clusters (namely cluster I to IV). RTA’s active site is surrounded by cluster III. Surprisingly, mAb IB2, which defines cluster III is the only antibody that recognized this immunodominant region. We previously showed that IB2 binds to helices C and G on the surface of RiVax. In this study, we sought to gain a better understanding of cluster III using a collection (21) of single domain antibodies (VHHs) that are derived from ricin immunized alpacas. To this end, I first produced and characterized RiVax (a safer version which is structurally identical to RTA) for its structural integrity since our main emphasis lies in identifying discontinuous/ conformational epitopes. Based on hydrogen exchange mass spectrometry (HX-MS) studies, VHHS recognized overlapping epitopes with four spatially distinct contact regions i.e. they were grouped into four subclusters (namely 3.1 to 3.4) within cluster III region. Subcluster 3.1 includes helices C and G. Subcluster 3.2 encompasses additionally helix B along with helices C and G. While subcluster 3.3 consists of helices B and G, subcluster 3.4 includes helices C, E and strand h. Of the 21 antibodies that we analyzed, only two, namely V1D3 and V6D4 have shown toxin neutralizing activity (TNA). Both neutralizing antibodies have strong binding affinity (sub nanomolar range) to the toxin and engaged a common secondary structural element, namely helix G as part of their epitope. The second part of my dissertation focusses on fibroblast growth factor-1 (FGF-1), a member of β-trefoil family of proteins. FGFs regulate a number of developmental process including mitogenesis, angiogenesis and homeostasis etc. Due to their wide range of biological activities, FGFs has been of interest in several clinical applications. In particular, wound healing has generated considerable interest. Studies have shown that several polyanions (sulfated and phosphorylated) have increased the thermal stability of FGF-1 by 15-30oC. In this study, we sought to identify the binding sites of the polyanions. In particular, we studied two sulfated (heparin, low MW heparin) and two phosphorylated (phytic acid and ATP) polyanions. Using HX-MS, we examined the local dynamics as well as binding sites of the polyanions. For local dynamics, we identified strand 4 and 5 and the turn connecting them to be most flexible which agrees with previous NMR studies. On the other hand, strands 8, 9 and 10 appear to be more rigid which is consistent with crystallographic B factors as well as local dynamic studies conducted by NMR. Crystal studies have shown that heparin binds to N-terminal Asn18 and to C-terminal Lys105, Tryp107, Lys112, Lys113, Arg119, Pro121, Arg122, Gln127 and Lys128 indicating electrostatic forces as the dominant interactions. Heparin binding as determined by HX-MS is consistent with the crystallography data. We find other polyanions tested bind in a similar manner to heparin, primarily targeting the turns in the lysine rich C-terminal region of FGF-1 along with two distinct N-terminal regions that contains lysines and arginines/ histidines. This confirms the interactions between FGF-1 and polyanions are primary directed by electrostatics.
en
Copyright held by the author.
Pharmaceutical sciences
B CELL EPITOPE MAPPING OF RIVAX, A CANDIDATE RICIN VACCINE ANTIGEN
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/27853/1/Angalakurthi_ku_0099D_16258_DATA_1.pdf
File
MD5
b2b5c2c9b1817a99293e686a2c446c34
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Angalakurthi_ku_0099D_16258_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/27853/2/Angalakurthi_ku_0099D_16258_DATA_1.pdf.txt
File
MD5
22cdcc236c9f8bd05e0c93405bb69b99
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Angalakurthi_ku_0099D_16258_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/266702018-07-28T08:02:09Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
author
Nobles, William Lewis
2018-07-27T13:19:03Z
2018-07-27T13:19:03Z
1952
http://hdl.handle.net/1808/26670
This work is in the public domain and is available for users to copy, use, and redistribute in part or in whole. No known restrictions apply to the work.
Some potential chemotherapeutic agents derived from aralkyl ketones
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/26670/1/nobles_1952_3429131.pdf
File
MD5
75a5ceb8003891e8042e43ab07471dae
24561426
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nobles_1952_3429131.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/26670/2/nobles_1952_3429131.pdf.txt
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569b21997ceb2d39e54ca95eff6a333b
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nobles_1952_3429131.pdf.txt
oai:kuscholarworks.ku.edu:1808/239272018-01-31T20:07:47Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Laird M
author
Zhang, Ti
cmtemember
Krise, Jeff
cmtemember
Siahaan, Teruna J
cmtemember
Tolbert, Thomas
cmtemember
Yang, Xinmai
2017-05-07T16:38:48Z
2017-05-07T16:38:48Z
2015-05-31
http://dissertations.umi.com/ku:13832
http://hdl.handle.net/1808/23927
The early diagnosis of cancer can help direct the best treatment strategy and improve patients' survival. The unique and tunable properties of nanoparticles facilitate the development of diagnostic imaging tools for earlier diagnosis and disease staging, and they can provide fundamental information on the pathological process. Nanoparticle probes have demonstrated to have numerous advantages over single molecule-based contrast agents, such as tumor-targeted delivery via the enhanced permeability and retention (EPR) effect, prolonged systemic circulation times to enhance imaging contrast efficiency, and facile surface modification for specific applications. The first part of this dissertation focuses on the development of radiation- damaged nanodiamonds (DNDs), a type of carbon-based nanoparticles, for the detection of solid tumors using a photoacoustic (PA) imaging technique. In chapter 2 of this dissertation, DNDs are proposed as ideal optical contrast agents for PA imaging in biological tissues due to their low toxicity and high optical absorbance. A new DND with very high NIR absorption was synthesized by He+ ion beam irradiation. These DNDs produced a 71-fold higher PA signal on a molar basis than similarly dimensioned gold nanorods, which were considered the "gold" standard agent for PA contrast agents. In order to develop DNDs as a molecularly-targeted contrast agent for high resolution and phenotype-specific detection of breast cancer with PA imaging, in chapter 3, an anti- Human epidermal growth factor receptor-2 (HER2) peptide (KCCYSL) was conjugated to the surface of PEGylated DNDs. PA images demonstrated that DNDs accumulate in orthotopic HER2 positive tumors and completely delineated the entire tumor within 10 hours. Chapters 4 and 5 of this dissertation describe the development of a hyaluronic acid (HA) polymeric nanoparticle to deliver drugs for the locoregional treatment of head and neck squamous cell carcinoma (HNSCC). In chapter 4, a HA-pyropheophorbide a (PPa) conjugate was synthesized. The anti-cancer efficacy was improved compared to the intravenously administered PPa molecules, and it was demonstrated that it could be useful for in vivo locoregional photodynamic therapy of HNSCC. In chapter 5, a pH- tunable delivery platform of platinum-based anti-cancer drug was designed and synthesized to improve the therapeutic index. The systemic toxicity of cisplatin was significantly reduced due to the pH-controlled release of the active forms of Pt species. In chapter 6, a lanthanum label was non-covalently conjugated to HA polymer to track the in vivo bio-distribution of HA in HNSCC tumors and organs that are responsible for the elimination of nanoparticles. In the last chapter, an enzymatic N-deacetylation method was applied in the modification on HA. New synthetic routs were explored to prepare HA derivatives for anti-cancer drug delivery to meet specific needs with retained HA characteristics.
en
Copyright held by the author.
Pharmaceutical sciences
Nanotechnology
Acoustics
Chemistry
Materials Science
Nanoscience
Polymer Chemistry
Engineered Nanomaterials for Targeted Imaging and Therapy
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/23927/1/Zhang_ku_0099D_13832_DATA_1.pdf
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URL
https://kuscholarworks.ku.edu/bitstream/1808/23927/2/Zhang_ku_0099D_13832_DATA_1.pdf.txt
File
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8ae2e5b40dc6f548468e6d055f5336b9
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oai:kuscholarworks.ku.edu:1808/135612020-10-16T14:41:40Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Alsenaidy, Mohammad A.
cmtemember
Middaugh, C. Russell
cmtemember
Tolbert, Thomas
cmtemember
Siahaan, Teruna J.
cmtemember
Desaire, Heather
2014-04-18T21:24:38Z
2014-04-18T21:24:38Z
2013-12-31
http://dissertations.umi.com/ku:13133
http://hdl.handle.net/1808/13561
Comparability assessments are frequently performed during biopharmaceutical drug development to evaluate the effects of manufacturing process changes on the structural integrity, safety and efficacy of candidate protein drug products. Physiochemical analytical evaluations (an essential element of any comparability exercise) involve multiple assessment techniques mapping the different aspects of protein structural integrity (primary and higher-order structures). Although significant advances in regards to primary structure evaluations have been made including peptide and oligosaccharide mapping techniques combined with mass spectrometry, the need for more sensitive approaches for the evaluation of higher order structures of proteins, especially in their final pharmaceutical dosage forms, remains an important challenge. In this dissertation, the ability of using multiple protein conformational stability studies (combined with novel data visualization approaches) as surrogates for evaluating and comparing different proteins's higher-order structure are explored in the context of comparability. Empirical phase diagrams (EPDs) and radar charts, constructed using large data sets from high throughput, lower-resolution biophysical techniques, are used to detect major (point mutations of FGF-1) and minor (different glycosylation patterns of an IgG1 mAb and Fc molecules) structural differences between proteins. In addition, for the IgG1 Fc glycoforms expressed in yeast, the effect of N-linked glycosylation site occupancy, as well as the effect of different charge states in various nonglycosylated forms, within the CH2 domain was examined. Using this approach, differences in conformational stability were detected under stress conditions that did not necessarily detect structural integrity differences in these proteins in the absence of these stresses. Thus, an evaluation of conformational stability differences may serve as an effective surrogate to monitor more subtle differences in higher-order structure between protein samples as part comparability assessments.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Biophysics
Comparability
Conformation
Glycosylation
Proteins
Applicability of Using Physical Stability Data and Advanced Visualization Methods in Protein Comparability Studies
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/13561/1/Alsenaidy_ku_0099D_13133_DATA_1.pdf
File
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Alsenaidy_ku_0099D_13133_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/13561/2/Alsenaidy_ku_0099D_13133_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/261522018-04-19T20:12:06Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory
advisor
Dhar, Prajnaparamita
author
Napolitano, Lorena Rodriguez Antunez
cmtemember
Paul, Arghya
cmtemember
Siahaan, Teruna
cmtemember
Volkin, David
2018-03-09T22:30:33Z
2018-03-09T22:30:33Z
2017-05-31
http://dissertations.umi.com/ku:15363
http://hdl.handle.net/1808/26152
Adjuvants are commonly included in vaccines and have been invaluable in making them safer and more robust. Despite their prolific use, adjuvant mechanisms of action remain poorly understood. Many receptor-mediated mechanisms have been proposed for adjuvants, and many likely contribute to their mechanisms of action, but several adjuvants also interact with the plasma membrane. Although few have considered how lipid-mediated interactions contribute to adjuvanticity, previous studies suggested aluminum-based adjuvants (ABAs) have high affinity for sphingomyelin and cholesterol, which allowed them to activate dendritic cells exclusively through lipid sorting. This dissertation sought to understand how lipid interactions contribute to the immunostimulatory properties of adjuvants. The membrane interaction of Alhydrogel (AH) and Adju-Phos (AP) was initially investigated in a simple lipid monolayer representative of the outer leaflet of the plasma membrane. AH and AP interacted with the model monolayer and promoted lipid clustering, although the physiochemical properties of each adjuvant caused them to interact differently. In a more complex lipid system containing sphingomyelin and cholesterol, the lipid interaction behavior was consistent and revealed AH and AP stabilized sphingomyelin- and cholesterol-rich lipid domains even in the presence of an antigen. Lipid raft clustering observed in dendritic cells exposed to ABAs in vitro was reminiscent of domain clustering observed in the monolayer and corresponded to conditions which enhanced cell activation, suggesting membrane interactions and lipid sorting could indeed contribute to ABA mechanisms of action. Lipid-interactions were also considered while designing an adjuvant-based antigen-specific immunotherapy (ASIT). An MF59-analog (MF59a) made in our lab was selected to co-deliver ovalbumin and dexamethasone based on its ability to solubilize dexamethasone, extend its release, and enhance its membrane permeability and internalization. The combination of MF59a, ovalbumin, and dexamethasone inhibited several pro-inflammatory cytokines in dendritic cells and ovalbumin-educated splenocytes, and proved emulsion adjuvants could provide an ideal vehicle to create targeted, tolerizing ASITs. Therefore, lipid interactions can provide valuable insight while selecting the physiochemical properties of an adjuvant for pro- and anti-inflammatory applications. Our results provide compelling evidence that lipid interactions participate in adjuvant mechanisms of action, and should be considered when developing novel vaccines and adjuvants.
en
Copyright held by the author.
Pharmaceutical sciences
Adjuvant
Drug Delivery
Immunotherapy
Lipids
Mechanism of action
Membrane
Adjuvant Interactions with Lipid Membranes and Their Effect on Cellular Immune Responses
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/26152/1/Napolitano_ku_0099D_15363_DATA_1.pdf
File
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URL
https://kuscholarworks.ku.edu/bitstream/1808/26152/2/Napolitano_ku_0099D_15363_DATA_1.pdf.txt
File
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oai:kuscholarworks.ku.edu:1808/216422018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Berkland, Cory
author
Gochioco, Kim
cmtemember
Stobaugh, John
cmtemember
Alvarez-Nunez, Fernando
2016-10-11T16:52:46Z
2016-10-11T16:52:46Z
2014-08-31
http://dissertations.umi.com/ku:13507
http://hdl.handle.net/1808/21642
Lactose is a widely used excipient in the pharmaceutical industry. It exists as anhydrous, alpha- and beta- monohydrate forms, which can be either crystalline or amorphous. Commercially available lactose comes in various grades differentiated by physical forms as well as modifications such as particle size. These characteristic modifications enable formulation and processing. Lactose grades for direct compression applications for example, contain various concentrations of crystalline and amorphous content. The mixture of forms exhibit unique material compaction properties that facilitate performance within formulations. Lactose is infrequently used in large concentrations for dry granulation processes because alpha-lactose monohydrate exhibits relatively poor binding properties and consolidates mainly by fragmentation due to its `brittleness'. Though this is true of crystalline lactose, previous direct compaction research has found that amorphous lactose is known to be more compressible than its crystalline form. This research aims to characterize the material properties of a directly compressible lactose monohydrate, Flowlac 100 containing high crystalline and high amorphous content; and to compare the fundamental differences in mechanical properties when manufactured by dry granulation via a roller compaction emulator. Ribbon properties such as tensile strength and solid fraction were measured, and the subsequent mechanical properties of tablets evaluated. Additionally, model drug formulations containing a very brittle drug, paracetamol, were manufactured into ribbons with high crystalline and high amorphous lactose. Subsequent tablettability was also evaluated. Results from this research suggest that amorphous lactose offers advantages over its crystalline counterpart such as an increased ribbon tensile strength under lower compression forces. A formulation containing amorphous lactose and a poorly compressible model drug manufactured through a roller compaction process resulted in acceptable tablets with improved friability over the crystalline formulation.
en
Copyright held by the author.
Pharmaceutical sciences
Physical chemistry
Amorphous
Crystalline
Lactose
Roller Compaction
The Effect of Crystalline and Amorphous Lactose on Mechanical Properties of Roller Compaction Ribbons and Tablets
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21642/1/Gochioco_ku_0099M_13507_DATA_1.pdf
File
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Gochioco_ku_0099M_13507_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21642/2/Gochioco_ku_0099M_13507_DATA_1.pdf.txt
File
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81ade591932a131cd786fa7728d0e4e6
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oai:kuscholarworks.ku.edu:1808/295462020-10-13T20:40:33Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B.
author
Hu, Yue
cmtemember
Weis, David D.
cmtemember
Siahaan, Teruna
cmtemember
Hageman, Michael
cmtemember
De Guzman, Roberto N.
2019-09-06T19:28:12Z
2019-09-06T19:28:12Z
2019-05-31
http://dissertations.umi.com/ku:16383
http://hdl.handle.net/1808/29546
https://orcid.org/0000-0003-2505-2731
ABSTRACT Monoclonal antibodies (mAbs) have become a class of therapeutic protein-based drugs of high importance for treating numerous human diseases. As a complex, delicate three dimensional molecule, a mAb can be sensitive to ambient environments and thus often display colloidal/conformational instability during manufacturing, storage, and administration. The use of formulation strategies, such as employing specific excipients and/or particular solution conditions (e.g., pH and buffers), can significantly improve a mAb’s pharmaceutical stability properties. In this Ph.D. thesis research work, both formulation/storage stability as well as stability during in vitro models of mAb administration in vivo are evaluated with two different of classes of immunoglobulin molecules (IgG and IgA). In addition, the effect of specific classes of excipients and solution conditions are examined by using a wide variety of physicochemical and immunological binding analytical techniques. Specifically, the second and third chapters of the Ph.D. thesis work focus on the formulation development of high-concentration mAb dosage forms for subcutaneous (SC) injections. Reversible self-association (RSA) of mAbs, which is primarily due to intermolecular protein-protein interactions (PPIs) between mAb molecules, has emerged as an important formulation challenge in terms of significantly increasing solution viscosity and turbidity as well as initiating phase separation. In these two chapters, two different human IgG1 molecules (mAb-J and mAb-C), which showed strong RSA propensity at relatively high protein concentrations, were comprehensively studied to better understand their solution properties and molecular behaviors by both biophysical techniques as well as hydrogen-deuterium exchange mass spectrometry (HX-MS). The aim is to not only characterize mAb molecular properties and solution behavior at relatively high protein concentrations, but also to develop a better mechanistic understanding by identifying peptide segments within the mAb involved PPIs in solution. In these two studies, both elevated solution viscosity and turbidity as well as reduced relative solubility and increased protein-protein interaction propensity (as measured by light scattering profiles and observations of phase separation) were determined for two different mAbs (mAb-J and mAb-C) at comparatively high protein concentrations. Concomitantly, based on the amino acid sequence of each mAb’s RSA sites (as determined by lyophilization-reconstitution-based HX-MS methodology), two different dominant non-covalent forces (electrostatic and hydrophobic) are proposed to be the major driving force for PPIs of the two different mAbs (consistent with previous results). More importantly for this work, varying effects of different excipients were investigated particularly for their ability of promote or disrupt PPIs of each mAb. For mAb-J (electrostatic driven RSA), selected ionic excipients showed the ability to disrupt liquid-liquid phase separation and reduce intermolecular interactions to varying extents, with arginine hydrochloride possessing the highest efficiency. For mAb-C (hydrophobic driven RSA), opposing effects were observed for sodium sulfate versus selected hydrophobic additives (e.g., specific salts, amino acids, solvents), showing both enhanced and reduced PPI propensity, respectively. In both studies, not only was the RSA of mAbs shown to be mAb concentration dependent, but the excipient’s ability to mitigate the RSA of mAbs RSA also displayed an excipient concentration dependent pattern. The fourth chapter focuses on the possibility of using various classes of mAbs, including secretory IgA (sIgA) and IgG1, as potential drug candidates for oral delivery to prevent enteric diseases in infants. Specifically, the use of mAbs against enterotoxigenic Escherichia coli (ETEC) is examined with the idea that passive immunization by pathogen-specific immunoglobulins, by oral delivery to infants, is promising approach to provide “instant” protection against ETEC. Secretory IgA (sIgA) is of particular interest because it is naturally found in the mucosal surfaces within the GI tract, is relatively more resistant to proteolysis by digestive enzymes (vs. IgG), and can protect against enteric bacteria by directly neutralizing virulence factors. In this study, three different mAbs, (sIgA1, sIgA2 and IgG1) against heat labile toxin (LT, one of the major virulence factors of ETEC), were used as a model for developing analytical techniques to characterize the structural integrity of the mAbs and to assess their stability profiles under various solution conditions (using physicochemical and immunochemical binding assays). In this work, very different total carbohydrate levels and N-linked glycosylation oligosaccharide composition profiles were observed between sIgAs and IgG1 made from CHO cell lines. According to SDS-PAGE, SE-HPLC, and SV-AUC results, heterogeneous mixtures of higher molecular weight species were observed for sIgAs, while IgG1 samples showed less heterogeneity with more than 90% monomer in solution. The overall physical stability results at both pH 7.2 and pH 3.0 demonstrated that both sIgA1 and sIgA2 were more stable than IgG1, with sIgA1 displaying the best stability profile. The relative solubility profile of each molecule was pH dependent with higher solubility noted at the lower pH. Furthermore, an in vitro digestion model was adapted in the laboratory to mimic in vivo oral gastric degradation conditions using minimal material, and was utilized to monitor the oral delivery stability of the three mAbs. It was shown that F(ab’)2 was the major digestion product by pepsin digestion. Both sIgAs displayed better resistance to degradation by proteases at low pH compared to IgG1. Moreover, the sIgAs showed greater retention of LT-antigen binding activity than that of IgG1, confirming the superior pharmaceutical properties of sIgAs for oral delivery. In summary, we hope to use the information gained by these preformulation characterization studies for the long-term goal to design stable, low-cost liquid formulations for oral delivery of sIgAs to protect against enteric diseases currently affecting infants in the developing world.
en
Copyright held by the author.
Pharmaceutical sciences
Characterization, Stabilization and Formulation Design of IgG and Secretory IgA Monoclonal Antibody Candidates during Storage and Administration
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29546/1/Hu_ku_0099D_16383_DATA_1.pdf
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oai:kuscholarworks.ku.edu:1808/216692018-01-31T20:07:47Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Asmus, Christopher Erik Helmut
cmtemember
Lunte, Susan
cmtemember
Stella, Valentino
cmtemember
Stobaugh, John
cmtemember
Rivera, Mario
2016-10-11T19:32:56Z
2016-10-11T19:32:56Z
2015-05-31
http://dissertations.umi.com/ku:14015
http://hdl.handle.net/1808/21669
The degradation pathway of hydrogen peroxide (H2O2) with sodium pyruvate elucidates the formation and breakdown of an intermediate formed during the reaction. Sodium pyruvate is a potential base for the creation of a peroxide scavenger. It readily reacts with H2O2 to yield sodium acetate, carbon dioxide and water as final products. A low temperature nuclear magnetic resonance protocol has been developed in order to observe the formation and breakdown of a proposed intermediate, 2-hydroxy-hydroperoxy-propanoate. Samples of 13C-enriched sodium pyruvate were used to verify the formation of the intermediate and identify its structure by the heteronuclear multiband correlation spectroscopy NMR method. The observed chemical shifts have been compared with the predicted chemical shifts obtained from density functional theory calculations. In order to calculate the activation parameters of the formation and breakdown of the intermediate a low temperature 13C-NMR protocol has been developed that allowed to record intergable spectra of sodium pyruvate, the intermediate and the products formed by the reaction with H2O2 at various temperatures. The integrated data have been plotted vs. time which allowed to calculate the individual rate constants of the reaction steps at various temperatures. Based on the rate constants the activation parameters, the enthalpy, entropy and free energy of the transition states of the formation and breakdown of the intermediate have been calculated. The metal-catalyzed pathway of hydrogen peroxide is dealing with the effect of hydroxyl radicals created by the Fenton reaction and their potential to oxidize the disulfide bridge of small peptides. Based on the reduction potential, which is an indicator for the oxidizability by radicals, disulfide bridges in a peptide or protein are more facile targets for radical attack than methionine (Met) which is known to be easily oxidized by reactive oxygen species. The effects of the Fenton reaction on the peptides pressinoic acid (PA), oxytocin (Oxt) and a custom made peptide containing a disulfide bridge have been studied. The experiments showed that the aromatic residues tyrosine (Tyr), which present on both PA and Oxt and Phenylalanine (Phe), which occurs on PA as well as arginine (Arg) located on the custom made peptide have been subject to hydroxylation by the ROS created through the Fenton reaction. No modification of the disulfide bridge such as oxidation, disulfide scrambling or formation of new carbon-sulfur bonds was detected on these peptides after the Fenton reaction has been applied.
en
Copyright held by the author.
Chemistry
Pharmaceutical sciences
Analytic
hydroxyphenylalanine
Intermediate
NMR
The reaction pathways of hydrogen peroxide in the presence of scavengers and its transition metal catalyzed oxidation of disulfide bridge containing peptides
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21669/1/Asmus_ku_0099D_14015_DATA_1.pdf
File
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https://kuscholarworks.ku.edu/bitstream/1808/21669/2/Asmus_ku_0099D_14015_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/216502018-01-31T20:07:47Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Telikepalli, Srivalli
cmtemember
Middaugh, Charles R
cmtemember
Siahaan, Teruna J
cmtemember
Tolbert, Thomas J
cmtemember
Deeds, Eric J
2016-10-11T17:18:09Z
2016-10-11T17:18:09Z
2014-12-31
http://dissertations.umi.com/ku:13723
http://hdl.handle.net/1808/21650
One of the predominant concerns with protein therapeutics is their tendency to aggregate at various stages of protein production, purification, filling, transportation, and administration. This occurrence has biological significance; while there is no definite, general cause and effect relationship for all protein drugs, many studies suggest that protein aggregates in certain biotherapeutics can decrease efficacy or cause untoward immune responses in human patients. Current research suggests that certain types of protein aggregates may be more immunogenic than others. In this Ph.D. thesis research work, three different IgG monoclonal antibodies (2 IgG1 mAbs, one in solution and one in lyophilized form and one IgG2 mAb in solution) were stressed by a variety of different conditions and the resulting aggregates and particles were characterized using a broad array of methods. Some of the characteristics examined included aggregate/ particle size, count, and morphology, as well as the covalent cross-linking and structural integrity of the protein within the aggregates. In all cases, accelerated stability studies, similar to those performed in the biopharmaceutical industry, were utilized to generate aggregates. In the first study, an IgG1 mAb in solution was subjected to freeze-thaw, shaking, stirring, and heat stress in the presence and absence of NaCl. Depending on the solution and stress conditions, very different types of aggregates and particles formed. In the second study, an IgG1 mAb in lyophilized form was shaken to mimic worst-case shipping condition, which led to extensive cake breakage and upon reconstitution, displayed increased turbidity and subvisible particles compared to the unstressed sample. This study highlights potential stability concerns regarding lyophilized protein undergoing various shipping processes. In the third study, the impact of protein particle size on inducing an early and late phase immune response in an in-vitro assay using human peripheral blood mononuclear cells (PBMC) was investigated. Stir-induced IgG2 mAb aggregates were size-enriched using fluorescence activated cell sorting (FACS) and tested for their ability to induce PBMC cytokine responses, at two phases of the immune response. The size-enriched particles were simultaneously characterized to determine traits, other than size, that may be responsible for the in-vitro assay responses. Amorphous subvisible particles 5-10 μm in size, containing protein with partially altered secondary structure and elevated surface hydrophobicity (compared to controls), and containing elemental fluorine, displayed relatively elevated cytokine release profiles compared to other size ranges. Studies carried out as part of this Ph.D. thesis highlight the importance of 1) comprehensively characterizing protein aggregates and particles to better understand their formation, 2) the need for closer evaluation of the effects of shaking stress on lyophilized protein formulations during shipping, and 3) studying the potential biological implications of a subset of protein particles in an in vitro system, along with developing a better understanding these aggregate's physicochemical properties, should provide improved insights into why some protein aggregates elicit higher immune responses than others in vivo.
en
Copyright held by the author.
Pharmaceutical sciences
Monoclonal antibodies
Protein
Protein Aggregation
Protein Particles
Subvisible Particles
Aggregation of IgG mAb Biotherapeutics: Sources, Methods of Characterization, and Biological Implications
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21650/1/Telikepalli_ku_0099D_13723_DATA_1.pdf
File
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URL
https://kuscholarworks.ku.edu/bitstream/1808/21650/2/Telikepalli_ku_0099D_13723_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/61752020-07-28T13:23:06Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Laurence, Jennifer S.
author
Skinner, Andria L.
cmtemember
Middaugh, C. Russell
cmtemember
Schöneich, Christian
cmtemember
Rivera, Mario
cmtemember
DeGuzman, Roberto
2010-05-03T00:39:43Z
2010-05-03T00:39:43Z
2009-12-15
http://dissertations.umi.com/ku:10674
http://hdl.handle.net/1808/6175
Phosphatase of regenerating liver (PRL-1) has gained attention as an important therapeutic target because of its involvement in cancer and metastasis, where it promotes proliferation and cell motility. The protein is found at high concentration in numerous cancer tissues and when over-expressed induces cellular transformation. Elevated levels of PRL-1 have been shown to trigger metastasis and to promote cellular transformation and tumorigenesis. Because its enzyme activity contributes to both tumorigenesis and metastasis, this protein is an attractive target for therapeutic intervention. The problem with ubiquitously inhibiting PRL-1 is that this enzyme is also essential to cell survival and tissue regeneration under normal physiological conditions. Inhibition may result in nonspecific and unwanted cell death of healthy tissues. Targeting only the overactive form of an enzyme would provide a reasonable resolution to this problem, but it is currently unknown how PRL-1 prompts proliferation in some cells and differentiation in others. The long-term goal of this project is to identify the crucial structural and dynamic features that support the enzymatic activity of PRL-1 and characterize the different forms to identify ones appropriate to target for therapeutic intervention. In this work, we have shown that the full-length unmodified form of PRL-1 is primarily inactive based on its determined reduction potential (-364.3 ± 1.5 mV) and that in vivo, activation is likely conferred through a posttranslational modification at the C-terminus. Using an assortment of biophysical techniques, we have also shown that a mutant form of PRL-1 (PRL-1-C170S/C171S) is reduced and active and can serve as a model for posttranslationally modified PRL-1 at this site. A second goal of this dissertation project is to use PRL-1 as a model system for studying protein stability. An understanding of the forces that contribute to protein stability is crucial to the development of new biotechnology products with improved half-lives and lower immunogenicity. Because proteins are held together by numerous weak interactions, understanding the mechanisms by which stabilization is achieved is important to the design of new biotechnology products that better resist unfolding and aggregation. Mechanistic information describing how specific interactions influence stability is lacking, in part because the techniques typically used to study inherent stability do not provide sufficient detail. We used high-resolution solution NMR to examine the details of one aspect of stability in PRL-1. It is well-established that the oxidation state of cysteine residues in proteins are critical to overall physical stability. The presence of disulfide bonds most often imparts thermodynamic stability, and as such, engineered disulfide bonds have become a means for improving the viability of protein therapeutics. In some cases, however, disulfide bonds can diminish stability. PRL-1 has two discernable stable states, one of which contains a disulfide bond (oxidized, inactive) and is slightly less stable than the one that does not (reduced, active). To understand how the reduced form compensates for the loss of the disulfide bond, a series of mutants were analyzed that disrupted disulfide bond formation in distinct ways. The physical stability of each variant is unique with respect to the others, indicating that the stability of the whole protein depends on a combination of local, synergistic interactions with the Cys side chains. High-resolution solution NMR was used to provide site-specific and mechanistic information about how each interaction influences the protein's physical stability. This analysis reveals several key structural components that contribute to PRL-1's overall stability in the absence this disulfide bond. The results provide insight to explain how the reduced protein compensates for the loss of this structural feature, which has implications for its function in vivo, and how local instability may lead to aggregation.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Physical chemistry
Chemistry
Biochemistry
Drug screening
Nmr
Prl-1
Redox regulation
Stability
Structure activity relationship
Using High-Resolution NMR to Examine the Components that Contribute to the Activity and Stability of Phosphatase of Regenerating Liver (PRL-1) and Their Dependence on the Redox State of Cysteine Residues
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6175/1/Skinner_ku_0099D_10674_DATA_1.pdf
File
MD5
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Skinner_ku_0099D_10674_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6175/2/Skinner_ku_0099D_10674_DATA_1.pdf.txt
File
MD5
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346637
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Skinner_ku_0099D_10674_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/106232020-09-22T13:45:59Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Thakkar, Santosh V.
cmtemember
Middaugh, C. Russell
cmtemember
Siahaan, Teruna J.
cmtemember
Laurence, Jennifer S.
cmtemember
Volkin, David B.
cmtemember
Weis, David D
2013-01-20T15:03:37Z
2013-01-20T15:03:37Z
2012-12-31
http://dissertations.umi.com/ku:12567
http://hdl.handle.net/1808/10623
Proteins, such as immunoglobulins, are inherently dynamic molecules with unique biological functions. The intra- and intermolecular interactions that govern the dynamic nature and function of immunoglobulins may also influence their stability. A molecular understanding of interrelationship between dynamics, function and conformational stability of immunoglobulins, both in solution and in presence of co-solutes, can be important for their pharmaceutical development. In addition, it is important to understand the differences in any such correlations between closely related immunoglobulins. Furthermore, molecular interactions in immunoglobulins can be unique at low and high concentrations, which necessitate newer complementary approaches to investigate such complex systems. Therefore, a better understanding of interactions that govern protein structure, dynamics and conformational stability at low and high concentrations and in presence of excipients should aid in designing, optimizing and developing rational formulation conditions for protein based therapeutics. A variety of experimental methods sensitive to structure, dynamics and conformational stability of proteins in solution were employed in these studies. External perturbations such a change in pH, ionic strength and temperature were used to probe the response of proteins, both at low and high concentrations. Different monoclonal antibodies within IgG1 isotype were used to investigate interrelationships between protein dynamics and conformational stability in absence and presence of co-solutes. In addition, an ultraviolet spectroscopy based approach was developed to understand interactions modulating solution viscosity in high concentration immunoglobulin solutions. These studies provide evidence that immunoglobulins belonging to the same IgG1 subtype can have notable differences in their conformational stability, dynamics, aggregation propensity, hydration properties and their response to co-solutes. In addition, alterations in protein dynamics (at a global protein level and in local regions with differences in solvent exposures) by stabilizing or destabilizing excipients were found to modulate the conformational stability of a monoclonal antibody. Furthermore, it was determined that potential interactions and factors modulating solution viscosity at high protein concentrations may also result in changes in their extinction coefficients. The work presented in this dissertation provides evidence that factors modulating protein dynamics and those governing intra- and intermolecular interactions can influence the conformational stability, aggregation and viscosity of proteins in solution.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Biophysics
Aggregation
Excipient
Immunoglobulin
Protein dynamics
Stability
Viscosity
STUDIES ON THE CONFORMATIONAL STABILITY, DYNAMICS AND VISCOSITY OF IMMUNOGLOBULINS
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10623/1/Thakkar_ku_0099D_12567_DATA_1.pdf
File
MD5
ab01c0a5084a9ff53e2397f0c0e1db03
2275696
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Thakkar_ku_0099D_12567_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10623/2/Thakkar_ku_0099D_12567_DATA_1.pdf.txt
File
MD5
d23f71b57bd9556e682a6fee0b088d02
275521
text/plain
Thakkar_ku_0099D_12567_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/301992021-03-05T16:54:48Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John
author
Hartzel, Ian
cmtemember
Lacher, Nathan
cmtemember
Lunte, Susan
2020-03-28T20:50:26Z
2020-03-28T20:50:26Z
2019-12-31
http://dissertations.umi.com/ku:16789
http://hdl.handle.net/1808/30199
https://orcid.org/0000-0001-7947-533X
Disease caused by bacterial infections affect children and adults worldwide can be potentially life-threatening. Bacterial strains, such as Staphylococcus aureus and Streptococcus pnueumoniae (pneumococcus), express capsular polysaccharides on their surface, which act as a virulence factor for evading the immune system and are structurally unique depending on the serotype. Vaccines designed against the capsular polysaccharides have shown to be effective in reducing the incident rate of disease caused by bacterial injections. Glycoconjugate vaccines comprise large molecular mass bacterial capsular polysaccharides conjugated to a carrier protein, which helps activate T cells that trigger immunological memory functions. Un conjugated (free) carrier protein and polysaccharide are critical attributes typically included in analytical testing for glycoconjugate vaccines and must be monitored throughout the vaccine development process. High levels of free polysaccharide or carrier protein may be indicative of poor conjugation efficiency or product degradation caused by manufacturing inconsistencies, formulation, or storage conditions. In this work, we will present the development of an HPLC method to simultaneously quantitate free carrier protein and free polysaccharide in a glycoconjugate vaccine drug substance. This method would be developed for two S. aureus glycoconjugate drug substances, CP5-CRM197 and CP8-CRM197. Initial work focused on using hydrophobic interaction chromatography (HIC) as the mode of separation by utilizing the often-ignored separation space prior to the void volume. However, the separation proved to be difficult in a 1D format due to the complexity of the sample mixture and the chromatographic behavior of the glycoconjugate. Therefore, a 2D-LC approach was taken to separate and quantitate the free carrier protein and free polysaccharide in the two S. aureus glycoconjugate drug substances. This work focused on the development of SEC and RPLC methods, 2D-LC instrumentation design, 2D-LC method development, and assay performance. Results were then compared to results from current technologies in place based on capillary electrophoresis (CE) for the quantitation of free carrier protein and free polysaccharide to assess the feasibility of supporting manufacturing process and formulation development studies. In addition, this methodology was explored as a potential platform technology for monitoring free carrier protein and polysaccharide in other glycoconjugate vaccine projects in the development pipeline.
en
Copyright held by the author.
Pharmaceutical sciences
Method for Simultaneous Quantitation of Free Carrier Protein and Free Polysaccharide in Glycoconjugate Vaccines by High Performance Liquid Chromatography
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/30199/1/Hartzel_ku_0099M_16789_DATA_1.pdf
File
MD5
80f6fad2c89a4dfdeb0a94171afb86a1
31355576
application/pdf
Hartzel_ku_0099M_16789_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/30199/2/Hartzel_ku_0099M_16789_DATA_1.pdf.txt
File
MD5
b5a70ef385623c1f399b16ddcf07dda9
203171
text/plain
Hartzel_ku_0099M_16789_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/107702020-09-22T13:36:24Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Siahaan, Teruna J.
author
Laksitorini, Marlyn D.
cmtemember
Berkland, Cory J.
cmtemember
Tolbert, Thomas
2013-01-31T01:22:01Z
2013-01-31T01:22:01Z
2012-08-31
http://dissertations.umi.com/ku:12403
http://hdl.handle.net/1808/10770
We have developed linear cadherin peptides (i.e., HAV- and ADT peptides) that enhance brain delivery of drug molecules to the central nervous system (CNS). These peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells in the blood-brain barrier (BBB) to increase paracellular drug permeation. In this study, the goal was to design cyclic peptides (ADTC1, ADTC5, and ADTC6) derived from linear ADT6 (Ac-ADTPPV-NH2) to improve their stability and biological activity in improving paracellular delivery of drugs into the brain. The ADTC1 peptide (cyclo(1,8)Ac-CADTPPVC-NH2) was designed by adding two Cys residues at the N- and C-terminus of ADT6 peptide and a disulfide bond from thiol groups of the Cys residues. The ADTC5 peptide (cyclo(1,7)Ac-CDTPPVC-NH2) was derived from ADTC1 by deleting the alanine residue from the N-terminal region of ADTC1 and ADTC6. (Cyclo(1,6)Ac-CDTPPC-NH2) was constructed by deleting the valine residue from the C-terminal region of ADTC5. The results showed that ADTC1 has activity in inhibiting the resealing of the intercellular junctions of the MDCK cell monolayers similar to that of the linear ADT6, indicating that cyclization can maintain the peptide activity. The alanine residue deletion in ADTC5 does not reduce its activity compared to ADTC1 peptide, suggesting that the alanine residue does not have an important role in the activity of the peptide. In contrast, ADTC6 peptide does not have activity in inhibiting the junction resealing, indicating that the valine residue is important for peptide activity. ADTC5 inhibits the junction resealing of MDCK cell monolayers in a concentration-dependent manner with the saturation concentration above 0.4 mM and IC50 around 0.3 mM. Under the current experimental conditions, ADTC5 improves the delivery of 14C-mannitol to the brain about two fold compared to the vehicle negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide does not enhance the BBB passage of large polyethylene glycol molecules (i.e., PEG-1500 and PEG-40000) in an in situ rat brain perfusion model. In conclusion, formation of cyclic peptides can maintain cadherin peptide ability to modulate intercellular junctions of the BBB, and the primary sequence of ADT peptides is important for their biological activity.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Molecular biology
Adt
Blood-brain barrier
Cyclic cadherin peptide
Drug delivery
Intercellular junction modulation
Paracellular pathways
Design of Cyclic-ADT Peptides to Improve Drug Delivery to the Brain via Inhibition of E-Cadherin Interactions at the Adherens Junction
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/10770/1/Laksitorini_ku_0099M_12403_DATA_1.pdf
File
MD5
ab3eea5d7d909b89a1046048b383345c
339237
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Laksitorini_ku_0099M_12403_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10770/2/Laksitorini_ku_0099M_12403_DATA_1.pdf.txt
File
MD5
c5e6962379990eaaa0bf6c36aa20bed7
51777
text/plain
Laksitorini_ku_0099M_12403_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/298462021-03-05T16:53:56Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Hageman, Michael
author
Lou, Hao
cmtemember
Chung, John
cmtemember
Berkland, Cory
2019-12-10T20:50:25Z
2019-12-10T20:50:25Z
2019-08-31
http://dissertations.umi.com/ku:16734
http://hdl.handle.net/1808/29846
The study in this thesis systemically investigated the application of core/shell technique to improve powder compactability. A 28-run Design-of-Experiment (DoE) was conducted to evaluate the effects of the type of core and shell materials and their concentrations on tensile strength and brittleness index. Six machine learning algorithms were used to model the relationships of product profile outputs and raw material attribute inputs: response surface methodology (RSM), support vector machine (SVM), and four different types of artificial neural networks (ANN), namely, Backpropagation Neural Network (BPNN), Genetic Algorithm Based BPNN (GA-BPNN), Mind Evolutionary Algorithm Based BPNN (MEA-BPNN), and Extreme Learning Machine (ELM). Their predictive and generalization performance were compared with the training dataset as well as an external dataset. The results indicated that the core/shell technique significantly improved powder compactability over the physical mixture. All machine learning algorithms being evaluated provided acceptable predictability and capability of generalization; furthermore, the ANN algorithms were shown to be more capable of handling convoluted and non-linear patterns of dataset (i.e. the DoE dataset in this study). Using these models, the relationship of product profile outputs and raw material attribute inputs were disclosed and visualized.
en
Copyright held by the author.
Pharmaceutical sciences
The Application of Machine Learning Algorithms in Understanding the Effect of Core/Shell Technique on Improving Powder Compactability
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/29846/1/Lou_ku_0099M_16734_DATA_1.pdf
File
MD5
cfe0ef15f8f4529b667937cc1956adc3
1272937
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Lou_ku_0099M_16734_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29846/2/Lou_ku_0099M_16734_DATA_1.pdf.txt
File
MD5
9483ee761a2aee4c4c2ca4398b3952fc
50804
text/plain
Lou_ku_0099M_16734_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/43362020-07-22T13:07:05Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Stella, Valentino J.
author
Nti-Addae, Kwame Wiredu
cmtemember
Borchardt, Ronald T
cmtemember
Givens, Richard
cmtemember
Munson, Eric J.
cmtemember
Laurence, Jennifer S.
cmtemember
Forrest, Laird
2009-02-02T05:53:07Z
2009-02-02T05:53:07Z
2008-10-24
http://dissertations2.umi.com/ku:2750
http://hdl.handle.net/1808/4336
The synthesis, physicochemical characterization and evaluation of sulfenamide derivatives of antimicrobial oxazolidinones as prodrugs are described in this dissertation. Synthesis of sulfenamide derivatives described in this work involves the use of thiophthalimide intermediates. These thiophthalimide intermediates allow for a clean one step reaction, which requires less purification steps resulting in higher yields of sulfenamide products compared to a previously described synthetic route that incorporated the use of unstable sulfuryl chloride intermediates. The sulfenamide prodrugs undergo chemical conversion through the hydrolytic cleavage of the N-S bond during aqueous stability studies to release the parent drug molecule. However, insufficient aqueous stability characteristics may pose potential problems for future development of sulfenamide prodrugs as ready to use liquid formulations. The stability of the sulfenamide prodrugs was studied in the presence of small molecule thiols with varying thiol pKa. These studies showed that the thiolate ion was the species responsible for the nucleophilic attack on the sulfur atom of the N-S bond, leading to the cleavage of the bond to release the parent molecule and a mixed disulfide. Reactions of the sulfenamide prodrugs with thiol containing proteins such as human serum albumin and PRL-1 also resulted in the nucleophilic cleavage of the sulfenamide bond to release the parent molecule. The reactions of the sulfenamide prodrugs with small molecule thiols and thiol containing proteins led to the conclusion that in vivo conversion will occur via the nucleophilic attack of thiolate species. Attempts to study the permeability of the sulfenamide derivatives were hindered by the rapid conversion of the sulfenamide prodrugs to the parent molecule in the transport study setup. This rapid conversion is believed to be caused by the presence of thiol containing proteins on the surface of the Caco-2 cell monolayer and also within the cells. However, analysis of the initial permeability data shows that the sulfenamide prodrugs are contributing to the slight improvement of the permeability of the parent molecule.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Sulfenamide prodrugs
Synthesis and Physiochemical Characterization of Sulfenamide Prodrugs of Antimicrobial Oxazolidinones
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/4336/1/umi-ku-2750_1.pdf
File
MD5
e1817e13e1b212ee836a72573fb8ee13
2616497
application/pdf
umi-ku-2750_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/4336/2/umi-ku-2750_1.pdf.txt
File
MD5
558c6a6fc1d104fc620c645f7cfcb4e9
302937
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umi-ku-2750_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/61802020-07-27T15:35:02Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Esfandiary, Reza
cmtemember
Laurence, Jennifer S.
cmtemember
Siahaan, Teruna J.
cmtemember
Berkland, Cory J.
cmtemember
David, Sunil A.
2010-05-03T00:53:19Z
2010-05-03T00:53:19Z
2009-08-10
http://dissertations.umi.com/ku:10532
http://hdl.handle.net/1808/6180
Macromolecules, due to their large size and complexity are prone to a variety of physical and chemical degradations. Development of stable formulations that retain the macromolecule's stability and activity over its designated shelf life is therefore a crucial step in the production of such complexes as safe and effective therapeutics. One rapid and systematic formulation tool is the utility of the empirical phase diagrams (EPDs) which have enhanced our understanding of the response of the structure and stability of proteins to environmental perturbations. In the case of more complex macromolecular systems (e.g., multi-domain fusion proteins, large recombinant proteins, and viruses), however, the measured stability is presumably the sum of all components. This makes interpretations at the molecular level difficult. Herein, we have investigated the structural stability of three macromolecular systems of varying complexity to see if their structural stability can at least be partially understood in terms of the behavior of their individual domains and components. We have examined the effect of the observed structural alterations on the losses in activity. We have discussed how this information can be used in designing high throughput screening assays for identification of solution stabilizers for development of optimal formulations. The utility of the obtained information in interpretation of the biological functions of these systems in vivo is also evaluated. Empirical Phase Diagrams constructed based on techniques sensitive to transitions due to alterations of protein motions have been shown to provide information above and beyond that obtained by the static approach. Therefore, integration of techniques that detect extensive and subtle conformational alterations of proteins, as well as structural fluctuations into an EPD appears to be crucial. Herein, we show that plots of the temperature dependent 2nd derivative peak positions of aromatic residues have measurable slopes prior to protein unfolding and that these slopes are sensitive to the dielectric properties of the surrounding microenvironment. We further demonstrate that these slopes correlate with hydration of the buried aromatic residues in protein cores and can therefore be used as qualitative probes of protein dynamics.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Understanding Structural Stability of Pharmaceutically Relevant Macromolecular Complexes: A Biophysical and Biochemical Approach
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6180/1/Esfandiary_ku_0099D_10532_DATA_1.pdf
File
MD5
c6a397691adc57a769f7fe74431890fe
18509871
application/pdf
Esfandiary_ku_0099D_10532_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6180/2/Esfandiary_ku_0099D_10532_DATA_1.pdf.txt
File
MD5
dc884e51ae451d99c2dd078350b46ddc
314551
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Esfandiary_ku_0099D_10532_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/104222020-08-25T13:59:17Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Krise, Jeffrey P
author
Funk, Ryan S.
cmtemember
Stella, Valentino J.
cmtemember
Siahaan, Teruna J.
cmtemember
Forrest, Laird
cmtemember
Dobrowsky, Rick T
2012-11-26T20:33:36Z
2012-11-26T20:33:36Z
2011-12-31
http://dissertations.umi.com/ku:11804
http://hdl.handle.net/1808/10422
Lysosomes accumulate weakly basic amine-containing drugs (i.e., lysosomotropic amines) through an ion trapping-type mechanism and are capable of disrupting lysosomal structure and function. A common finding following treatment with hydrophobic amine-containing drugs is a cellular lipidosis marked by the lysosomal accumulation of lipids. The impact of this drug-induced lipidosis on the lysosomal accumulation of weakly basic amine-containing drugs is unknown. In this work, hydrophobic (logP 2) amine-containing drugs (imipramine, haloperidol, risperidone, chlorpromazine, lidocaine, bupivacaine, amiodarone, verapamil, propranolol) were found to cause a significant increase in the cellular accumulation of the lysosomotropic amine, LysoTracker Red (LTR). Imipramine was further found to specifically increase the cellular accumulation of amine-containing substrates of lysosomal ion trapping (LysoTracker Green, daunorubicin, methylamine, propranolol) but not compounds that don't accumulate by ion trapping in lysosomes, suggesting that the drug-induced lipidosis specifically increases the cellular accumulation of drugs that accumulate in lysosomes. Imipramine-induced accumulation of LTR occurred in a time- and temperature-dependent manner in agreement with an energy-dependent intracellular remodeling process that has been reported to coincide with induction of the cellular lipidosis. Prevention of the imipramine-induced lipidosis by treatment with 0.1% hydroxypropyl-ß-cyclodextrin or growth in lipoprotein-depleted media prevented the increased accumulation of LTR, suggesting the hyperaccumulation of LTR is secondary to the drug-induced lipidosis. Determination of lysosome specific accumulation of LTR in cells with or without an intact lysosomal pH gradient revealed that imipramine caused an approximately three-fold increase in the lysosome-specfic uptake of LTR. Previous reports have suggested that drugs accumulate following a cellular lipidosis through enhanced hydrophobic binding sites. However, these results are consistent with an increased aqueous volume of lysosomes resulting in increased drug accumulation. Theoretical calculations of lysosomal volume changes following imipramine treatment reveal an approximately 4-fold increase in apparent lysosomal volume. Therefore, drug-induced lipidosis is found to increase the cellular accumulation of amine-containing drugs by causing a marked increase in the lysosomal volume of cells. These findings have implications towards understanding how drugs can interact at the intracellular level. The ability of one drug to affect the distribution properties of a second is further hypothesized to result in drug-drug interactions.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Pharmacology
Toxicology
Ion trapping
Lysosomes
Lysosomotropic
Phospholipidosis
Ph partitioning
Vacuolization
Studies on the impact of amine-containing compounds on lysosomes
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10422/1/Funk_ku_0099D_11804_DATA_1.pdf
File
MD5
1139381766d0bc264e07925763c34021
22883083
application/pdf
Funk_ku_0099D_11804_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10422/2/Funk_ku_0099D_11804_DATA_1.pdf.txt
File
MD5
cad0eda29458ad882fef2349d7a406cd
292312
text/plain
Funk_ku_0099D_11804_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216482018-01-31T20:07:51Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Majumdar, Ranajoy
cmtemember
Weis, David D
cmtemember
Tolbert, Thomas
cmtemember
Siahaan, Teruna J
cmtemember
Deeds, Eric
2016-10-11T17:12:14Z
2016-10-11T17:12:14Z
2014-12-31
http://dissertations.umi.com/ku:13653
http://hdl.handle.net/1808/21648
Immunoglobulins are large multi-domain and multi-functional proteins that are increasingly being developed as biologic drugs to bind to a wide variety of therapeutic targets. The immunoglobulin G1 class of molecules represents the largest class of therapeutic monoclonal antibodies (mAbs) currently under preclinical and clinical development. One of the major challenges in developing antibodies as drugs is their physical instability caused by various processing, storage and handling related stresses which can lead to aggregation and loss of efficacy. Immunoglobulins are dynamic molecules whose motions are important for their biological function and stability. It is currently difficult to predict the effects of minor process or formulation changes on the higher order structure and dynamics of mAbs using currently available analytical techniques. Hence new analytical techniques are needed to better understand the effects of such changes on the structure and dynamics of mAbs, especially within pharmaceutical dosage forms containing excipients. This dissertation work explored the effects of certain pharmaceutical excipients and three sodium salts from the Hofmeister series on the changes in thermal stability, storage stability and local dynamics of an IgG1 mAb. Changes in local dynamics of the mAb were explored at peptide level resolution using hydrogen-deuterium exchange mass spectrometry. Preliminary correlations were established between changes in dynamics of particular segments in the CH2 domain of the IgG1 mAb and decreased thermal stability as well as higher aggregation propensity of the IgG1 mAb in presence of destabilizing excipients and salts. This dissertation work also explored the mechanism behind the relative decrease in physical stability due to YTE (M255Y/S257T/T259E) triple mutation in the CH2 domain of a different IgG1 mAb (that was shown in previous work to result in extended in-vivo half-life due to changes in interaction with FcRn receptors). The YTE mutation induced decreases in physical stability of the IgG1 mAb which correlated with changes in local dynamics of the same particular segment in the CH2 domain described above in the presence of destabilizing excipients and salts. Hence, changes in dynamics of specific local segments within the CH2 domain of IgG1 mAbs identified in this work may serve as a general indicator for changes in physical stability for other IgG mAb drug products. By better understanding the root causes of mAb physical destabilization, more rational design of antibody formulations and/or protein engineering approaches are now possible to improve the pharmaceutical stability properties of mAbs.
en
Copyright held by the author.
Pharmaceutical sciences
Analytical chemistry
Biophysics
hydrogen/deuterium exchange
mass spectrometry
monoclonal antibody
physical stability
protein aggregation
protein dynamics
UNDERSTANDING THE RELATIONSHIPS BETWEEN LOCAL DYNAMICS AND PHYSICAL STABILITY OF IgG1 ANTIBODIES: EFFECTS OF EXCIPIENTS, SALTS AND MUTATIONS
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21648/1/Majumdar_ku_0099D_13653_DATA_1.pdf
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Majumdar_ku_0099D_13653_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21648/2/Majumdar_ku_0099D_13653_DATA_1.pdf.txt
File
MD5
1d519c63ef08f901d85cad6df74c09b1
406935
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oai:kuscholarworks.ku.edu:1808/102172018-01-31T20:08:10Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Laurence, Jennifer S.
author
Toler, Maria
cmtemember
Volkin, David B.
cmtemember
Singh, Satish
cmtemember
Martin, Susan
2012-10-27T10:46:32Z
2012-10-27T10:46:32Z
2012-08-31
http://dissertations.umi.com/ku:12207
http://hdl.handle.net/1808/10217
The characterization of particulate matter, especially protein aggregates, in the sub-visible and visible size range has become an area of focus in the biopharmaceutical industry. This heightened focus is due, in part, to increasing concern around particles causing immunogenicity, and increased queries from regulatory bodies. There has been extensive research in this area, with many recent publications on related methodologies, mechanisms and influencing factors. Two areas of interest are the characterization of these particles using material sparing approaches and the effect of the presence of silicone oil particles on protein solutions. With the focus on high concentration drug products (¡Ý50 mg/mL), and the drive toward conserving drug product by producing fewer batches, there is a real need for characterization techniques that require less sample. In addition, there is significant interest by the regulatory agencies in obtaining information on particulate matter in biologic drug products over a broad range of sizes. Queries are being generated by the FDA and other regulatory bodies, asking for particle count and any additional compositional information. They are requiring the pharmaceutical industry to have a deeper understanding of the formation of protein particles as well as methods for monitoring a broad range of sizes, over the shelf life of the product. The propensity exists for increased protein aggregation at higher concentrations, yet companies are generating less sample material for testing during development. The focus of this dissertation was to develop approaches for characterizing protein aggregation (particulates) using minimal sample amounts. To develop validatable methods for ongoing drug product monitoring as well as more novel approaches to better understand the nature of particulate matter present in biologic drug products. Silicone oil is present in many drug product contact surfaces and was chosen for further study on the effect of protein aggregation. The methods developed during this research were utilized to characterize protein and/or silicone oil particles, and to provide differentiation between protein and non-protein particles.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Particle characterization
Sub-visible
Visible
Techniques to Improve the Characterization of Protein Particles in Biologic Drug Products
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/10217/1/Toler_ku_0099M_12207_DATA_1.pdf
File
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b062f2c1054da06ff32009ea5ca5876b
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Toler_ku_0099M_12207_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10217/2/Toler_ku_0099M_12207_DATA_1.pdf.txt
File
MD5
dbc3224f10ca6eef02d04817df3c403c
137085
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Toler_ku_0099M_12207_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/107032020-08-12T13:16:28Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Laird
author
Cai, Shuang
cmtemember
Krise, Jeffrey P.
cmtemember
Siahaan, Teruna J.
cmtemember
Berkland, Cory J.
cmtemember
Cohen, Mark
2013-01-20T18:19:22Z
2013-01-20T18:19:22Z
2011-05-31
http://dissertations.umi.com/ku:11596
http://hdl.handle.net/1808/10703
Many cancers, such as breast cancer, lung cancer, and head and neck cancer, preferentially metastasize via the lymphatic system prior to their systemic invasion. Conventional chemotherapy has limited penetration into the lymphatics due to its anatomy, because drug molecules have to diffuse from the blood capillaries into the surrounding tissues and further enter the lymph vessels to reach the diseased lymph nodes. Therefore, chemotherapy can be of limited benefit in treating lymph node disease. In addition, due to the systemic administration and wide distribution, conventional intravenous chemotherapy causes a variety of organ toxicities, including but not limited to: renal toxicity, cardiotoxicity, and hepatic toxicity. This limits its use in the clinic, expecially for the elderly or late-stage patients who cannot tolerate systemic toxicities. Therefore, there is a critical need to develop of a localized drug delivery platform that confines the anti-cancer drugs to the site of the disease. This dissertation focuses on the development of subcutaneously delivered drug platforms for the treatment of cancers that are known to be lymphatically metastatic. The goal is to improve the anti-cancer efficacy and reduce the non-specific organ toxicities of small molecule chemotherapeutic agents. To achieve this goal, three polymer-based anti-cancer conjugates: hyaluronan-cisplatin (HA-Pt), hyaluronan-doxorubicin (HA-DOX), and sugar star polymer-nitric oxide prodrug 1 (sugar-NO1), were synthesized, characterized, and evaluated in preclinical rodent models. The route of drug administration along with the controlled release of the drug from the platforms, both play an important role in improving the biopharmaceutical properties of these conjugates. This is demonstrated by the extended systemic rentention, as well as the elevated local accumulation of the drug in the draining lymph nodes of the tumor, when compared to standard intravenous chemotherapy. The HA-Pt and HA-DOX conjugates exhibited reduced renal toxicity and cardiotoxicity, respectively, relative to the conventional intravenous chemotherapy in rats. Because of the improved pharmarcokinetic and toxicological profiles of the polymer-drug conjugates, animals that were treated with the subcutaneous conjugates demonstrated enhanced inhibition of the tumor progression and increased survival rates. To understand the increased anti-cancer activity of the conjugates on a cellular level, the interaction and internalization of the nanocarriers into tumor cells was also investigated using a gold nanoparticle tagged HA-Pt conjugate and a fluorescently labeled HA-DOX conjugate. In the clinic, cisplatin and doxorubicin are often administered in combination with other anti-tumor agents as a "chemo cocktail" to prevent chemoresistance. Additionally, nitric oxide has been shown to improve the cytotoxicity of cisplatin therapy via a synergistic effect. Therefore, the development of a nitric oxide prodrug cisplatin combinational therapy, with increased anti-proliferative activity against cancer cells, was investigated; and it is also presented in this disssertation and compared to cisplatin treatment alone. In conclusion, this thesis work has led to the successful preclinical development of two localized drug delivery platforms and one promising candidate for the treatment of metastatic carcinomas. The motivation for drug delivery scientists to develop more efficacious and less toxic chemotherapies will be presented.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Oncology
Cancer
Chemotherapy
Drug delivery
Lymphatic system
Nanotechnology
Polymer
Development of lymphatic drug delivery platforms for the treatment of carcinomas
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10703/1/Cai_ku_0099D_11596_DATA_1.pdf
File
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Cai_ku_0099D_11596_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10703/2/Cai_ku_0099D_11596_DATA_1.pdf.txt
File
MD5
3aa782f98db920a09b4f08c722137a9d
301310
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Cai_ku_0099D_11596_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/241472018-01-31T20:07:47Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory
author
Northrup, Laura Ann
cmtemember
Siahaan, Teruna
cmtemember
Forrest, Laird
cmtemember
Volkin, David
cmtemember
Dhar, Prajna
2017-05-15T00:54:17Z
2017-05-15T00:54:17Z
2016-12-31
http://dissertations.umi.com/ku:14990
http://hdl.handle.net/1808/24147
Multiple Sclerosis (MS) is an autoimmune disease characterized by the breakdown of immune tolerance towards autoantigen in the myelin sheath surrounding the neurons. Current therapies for MS and other autoimmune diseases focus on treating the symptoms and not the cause of the disease. A major setback in improving current therapeutics for autoimmunity is the lack of antigen specificity. Successful antigen-specific immunotherapy (ASIT) would allow for improved treatment of autoimmune diseases. This thesis investigates the creation of ASIT for autoimmunity through the co-delivery of an immunomodulator and autoantigen. First, immunomodulatory peptides targeting the B7 costimulatory pathway and cell adhesion were tested for their ability to suppress a murine model of MS, experimental autoimmune encephalomyelitis (EAE), utilizing a co-delivery vehicle developed in our lab, soluble antigen arrays. Peptides targeting different surface markers were all found to suppress EAE when co-delivered with autoantigen, demonstrating the ability of different immunomodulators to create effective ASIT. Expanding upon the idea of combinational ASIT, eleven different small molecules immunomodulators were screened for properties indicative of autoimmune suppression in an antigen-specific splenocyte system. This screen revealed that several compounds, most notably dexamethasone, had the ability to skew the antigen-specific immune response towards autoimmune suppression. The ability of dexamethasone to act as an effective immunomodulator in ASIT for autoimmunity was confirmed in vivo in the treatment of EAE. Co-delivery of dexamethasone and autoantigen in an oil-in-water emulsion, incomplete Freund’s adjuvant, was found to suppress EAE and shift the immune response. Overall, the results presented dissertation provide evidence for the successful creation of ASIT for autoimmunity by combining immunomodulator and autoantigen.
en
Copyright held by the author.
Pharmaceutical sciences
Immunology
Biomedical engineering
antigen-specific immunotherapy
co-delivery
experimental autoimmune encephalomyelitis
multiple sclerosis
Co-Delivery of Immunomodulators and Autoantigen as Antigen-Specific Immunotherapy for the Treatment of a Murine Model of Multiple Sclerosis
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/24147/1/Northrup_ku_0099D_14990_DATA_1.pdf
File
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Northrup_ku_0099D_14990_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/24147/2/Northrup_ku_0099D_14990_DATA_1.pdf.txt
File
MD5
bd45c903e776c933b4dfc3d23b4fd5de
294050
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Northrup_ku_0099D_14990_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216452018-10-29T16:01:50Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Schoneich, Christian
author
Lei, Ming
cmtemember
Stobaugh, John
cmtemember
Kao, Yung-Hsiang
2016-10-11T17:01:39Z
2016-10-11T17:01:39Z
2014-12-31
http://dissertations.umi.com/ku:13745
http://hdl.handle.net/1808/21645
https://orcid.org/0000-0002-1247-1358
The last decade has witnessed a rapid growth in the development of protein pharmaceuticals for diagnostic and therapeutic purposes. The biopharmaceutical industry increasingly demands thorough characterization of protein conformation and conformational dynamics to ensure product quality and consistency. Here we present a chromatography-based method that is able to characterize protein conformation and conformational dynamics at peptide level resolution in a high-throughput manner. The surface lysine residues of the protein were labeled with a fluorescent dye prior to trypsin and Glu-C digestion. The resulting peptide maps were monitored by fluorescence detection and the peak areas of the respective peptides were normalized to protein concentration. The normalized fluorescence peak area for a specific peptide represents the individual lysine solvent accessibility. A higher normalized fluorescence peak area indicates higher solvent accessibility at a specific site. The identity of the peak of interested was determined by LC-MS/MS analysis. We first demonstrated this method is suitable for probing protein surface/conformation by studying the effect of deglycosylation on a recombinant monoclonal antibody (mAb), IgG 1. The results from this method were consistent with previous results obtained by H/D-exchange. We then applied our method to study the interaction of the mAb with a common excipient, polysorbate-20 (PS-20). The interaction between PS-20 and the mAb was generally weak. The presence of PS-20 increased the fluorescent labeling of several lysine residues on the mAb. These lysine residues localized near the protein domains of relatively high hydrophobicity. This result provides a first insight into PS-20-mAb interaction at peptide level resolution.
en
Copyright held by the author.
Chemistry
Fluorescent
labeling
mass spectrometry
protein structure
Using Lysine-Reactive Fluorescent Dye for Surface Characterization of a Monoclonal Antibody
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21645/1/Lei_ku_0099M_13745_DATA_1.pdf
File
MD5
d00d14e68bbc58abbcd549cea4b588a0
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Lei_ku_0099M_13745_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21645/2/Lei_ku_0099M_13745_DATA_1.pdf.txt
File
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7adffecf0cc6403669129e7fb2f2b7ef
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Lei_ku_0099M_13745_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/83982020-08-07T16:59:31Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stella, Valentino J.
author
Willcockson, Maren Gulsrud
cmtemember
Toteva, Maria
cmtemember
Stobaugh, John F.
2011-11-13T02:02:56Z
2011-11-13T02:02:56Z
2011-08-31
http://dissertations.umi.com/ku:11590
http://hdl.handle.net/1808/8398
BHT is a common antioxidant in pharmaceutical formulations and when oxidized it forms a quinone methide (QM). QM is a highly reactive electrophilic species which can undergo nucleophilic addition. This research investigated the kinetic reactivity of QM with water at various pH values and in the presence of sodium chloride and phosphate, acetate, and TAPS buffers. The presence of HCl, HClO4, NaOH, NaCl, and phosphate buffers resulted in simple first order kinetics for disappearance of QM and the formation of a single product (OH-adduct); the reaction was subject to strong acid/base catalysis. The presence of acetate and TAPS buffers resulted in complicated kinetics suggesting the formation of an additional product in equilibrium with QM. These results indicate adduct formation with other nucleophilic excipients is likely which has implications for both the drug product impurity profile and specifications. Due to these considerations BHT should be used with caution.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Organic chemistry
Physical chemistry
Adduct formation
Antioxidants
Bht
Butylated hydroxytoluene
Hydrolysis
Quinone methide
Reactivity of the Quinone Methide of Butylated hydroxytoluene in Solution
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/8398/1/Willcockson_ku_0099M_11590_DATA_1.pdf
File
MD5
f26529a0a2de2620dcff42d9a5ec9b1f
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Willcockson_ku_0099M_11590_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/8398/2/Willcockson_ku_0099M_11590_DATA_1.pdf.txt
File
MD5
c5a40150894b647752307ce6408163ac
74807
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Willcockson_ku_0099M_11590_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216262020-10-19T14:14:21Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Krise, Jeffrey P
author
Logan, Randall
cmtemember
Siahaan, Teruna J
cmtemember
Tolbert, Thomas
cmtemember
Volkin, David B
cmtemember
Prisinzano, Thomas
2016-10-11T15:21:49Z
2016-10-11T15:21:49Z
2013-12-31
http://dissertations.umi.com/ku:13112
http://hdl.handle.net/1808/21626
From a clinical perspective, a drug's pharmacokinetic properties (e.g., the volume of distribution, clearance, and half-life) are vitally important as these parameters are used to establish the proper dosing regimen necessary to achieve a desired drug exposure. Failure to properly account for changes to a drug's expected pharmacokinetic properties, whether perpetrated by pharmacological insult (drug-drug interaction) or a disease state, can result in an improper dosing regimen that either fails to achieve therapeutic drug levels or, conversely, can result in drug levels that reach toxic concentrations. Identifying conditions that can alter the expected pharmacokinetic properties of drugs is therefore immensely important. Previous work in our lab has shown that lysosomotropic drugs, i.e., drugs that preferentially accumulate within lysosomes due to an ion trapping-type mechanism, cause a marked expansion in the volume of lysosomes which can result in a drug-drug interaction involving lysosomes. Although this novel drug-drug interaction was well characterized the mechanistic basis explaining how it developed was not established. Within this work we have explored the cellular mechanisms underlying the development of the drug-induced expansion in lysosomal volume and the ensuing drug-drug interaction. Our data shows that the drug-induced expansion in lysosomal volume is achieved through a combination of reduced vesicle-mediated trafficking out of the lysosomes, the induction of autophagy, and the activation of lysosome biogenesis. We have additionally explored a structure activity relationship which implicates a drug's amphiphilicity and lysosomotropic properties as important features that correlate with their propensity to induce an expansion in lysosomal volume. Overall, the data presented in this work can be used to help explain the sources of variability seen in the pharmacokinetic properties of lysosomotropic drugs. In parallel to these studies we have also explored potential treatment strategies that can reduce the bloated lysosomal volume seen in cells with dysfunctional lysosomes. Using two cell models that exhibit dysfunctional lysosomes (lysosomotropic drug-treated cells or lysosomal storage diseased cells), we have examined how vitamin E helps to recover lysosomal volume. Our data indicates that vitamin E reduces both ion trapping-dependent (aqueous volume of lysosomes) and ion trapping-independent (lipid binding) drug accumulation mechanisms within cells. To our knowledge, this is the first report detailing that vitamin E reduces the aqueous volume of lysosomes. This finding is important as it helps to more fully explain how vitamin E is eliciting its positive effects within cells. Additionally, we have also examined a structure activity relationship of vitamin E and its ability to reduce lysosomal volume. Our data indicates that the physical structure of vitamin E, rather than its antioxidant properties, is the primary feature of vitamin E that correlates with its ability to reduce the bloated lysosomal volume seen in cells with dysfunctional lysosomes. Overall, this data can be used as a foundation to stage additional studies that could ultimately lead to the development of more potent and better drug-like molecules that could be used to treat lysosomal storage diseases and the toxic effects of lysosomotropic drug-treatments.
en
Copyright held by the author.
Pharmaceutical sciences
Cellular biology
Pharmacology
Cationic Amphiphilic Drugs
Drug distribution
Drug Drug interaction
intracellular distribution
Lysosome
Lysosomotropic
Studies on the mechanisms and consequences of drug-induced perturbations of lysosomal structure and function
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21626/1/Logan_ku_0099D_13112_DATA_1.pdf
File
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Logan_ku_0099D_13112_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21626/2/Logan_ku_0099D_13112_DATA_1.pdf.txt
File
MD5
4df8145f04e1e0682efa59956cd8ffb1
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Logan_ku_0099D_13112_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/302142021-03-05T19:03:26Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Siahaan, Teruna J
author
Kopec, Brian Matthew
cmtemember
Siahaan, Teruna
cmtemember
Wang, Michael
cmtemember
DeKosky, Brandon
cmtemember
Hageman, Michael
cmtemember
Zhao, Liqin
2020-03-29T16:41:26Z
2020-03-29T16:41:26Z
2019-12-31
http://dissertations.umi.com/ku:16943
http://hdl.handle.net/1808/30214
There are a large number of protein-based therapeutics (biologics) that are FDA approved and available on the market for a number of diseases, and the number of biologics being approved every year has tripled in the past two decades. Biologics are highly attractive as therapeutic options due to their safety and efficacy; however, of all the marketed biologics, only several proteins are FDA approved for treatment of CNS. This is due to efficacy limitation of most proteins in the CNS. One of the reasons is due to the presence of the blood–brain barrier (BBB), which selectively limits protein drugs from entering the brain. Although the BBB is critical for things such as maintaining proper concentration of ions and preventing infection as well as harmful toxins from entering the brain, its selectivity makes it difficult to deliver diagnostic and therapeutic agents into the brain. Only a small fraction (i.e., 2%) of marketed small drugs has appreciable penetration into the CNS. Thus, there is a large unmet need to improve drug delivery to the brain for treatment of brain diseases such as multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s, and brain tumors. Currently, drugs that are not able to cross the BBB are sometimes administered via direct cranial injection or cerebral spinal fluid infusion; however, these are relatively invasive methods and they increase the risk for CNS infections. The goals of this project were specifically to investigate (i) if BBB modulation via the cadherin cyclic peptide, ADTC5, could be used to deliver brain-derived neurotrophic factor (BDNF) across the BBB to treat an experimental autoimmune encephalomyelitis (EAE), a mouse model of MS; (ii) if ADTC5 could also be used to deliver BDNF to treat an aggressive mouse model for Alzheimer’s disease (i.e., APP/PS1 mice); and (iii) how ADTC5 can improve brain delivery a monoclonal antibody (mAbs) for evaluating its clearance from the brain in healthy mice. First, we observed that ADTC5 was able to significantly enhance the deposition of BDNF to have efficacies in the EAE and Alzheimer’s disease animal models. Compared to when BDNF was delivered alone or placebo, BDNF + ADTC5 improved clinical body scores and cognitive performance in EAE mice and APP/PS1, respectively. Additionally, both EAE and APP/PS1 mice that were treated with BDNF + ADTC5 showed increase levels of NG2 microglia, and EGR and ARC mRNA transcripts compared to BDNF alone or vehicle. In the EAE model, the NG2 glia was associated with increased levels of myelin. Second, we monitored monoclonal antibody (mAb) brain deposition and clearance after its brain delivery with ADTC5 peptide. In addition, the effect of ADTC5 in mAb depositions in other organs was also determined. We observed a rapid clearance of mAb from the brain after enhanced delivery by ADTC5 with two different phases. The estimated t1/2alpha and t1/2beta of IgG mAb were 0.34 ¬± 0.22 h and 65.50 ± 12.09¬ h, respectively. This clearance was heavily facilitated by the liver and ADTC5 did not affect antibody deposition into liver, spleen, kidney, lung, or heart. Overall, this project demonstrates a proof-of-concept that brain diseases can be effectively treated via brain delivery of therapeutic proteins using BBB modulation by cadherin peptides (e.g., ADTC5).
en
Copyright held by the author.
Pharmaceutical sciences
Alzheimer's
antibodies
BDNF
Blood–Brain Barrier
Multiple Sclerosis
Brain delivery of BDNF and a monoclonal antibody for the treatment of neurodegenerative animal models
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/30214/1/Kopec_ku_0099D_16943_DATA_1.pdf
File
MD5
f4474ba715d7119a72953c609ebba0b7
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Kopec_ku_0099D_16943_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/30214/2/Kopec_ku_0099D_16943_DATA_1.pdf.txt
File
MD5
5355e8c3699a0bc661a896050b5c4eef
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Kopec_ku_0099D_16943_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/114682020-09-29T14:03:46Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Munson, Eric J.
advisor
Stella, Valentino J.
author
Dempah, Kassibla Elodie
cmtemember
Stobaugh, John F.
cmtemember
Tolbert, Thomas
cmtemember
Gehrke, Stevin H.
2013-07-14T15:48:12Z
2013-07-14T15:48:12Z
2013-05-31
http://dissertations.umi.com/ku:12698
http://hdl.handle.net/1808/11468
The purpose of the work presented in this dissertation was to investigate the correlation between the particle size of crystalline active pharmaceutical ingredients (APIs) and their solid-state NMR (SSNMR) proton spin-lattice relaxation times (1H T1) using model compounds. Dicumarol and salicylic acid were selected as model compounds for this study. Crystalline samples of the model compounds containing particles with sizes ranging from 1 &um- 800 &um were prepared by sieving, spray-drying, and anti-solvent precipitation. The physical state and the particle size of the materials prepared were characterized. A model that describes the correlation observed between the 1H T1 time of the dicumarol and the salicylic acid materials and their particle size was proposed. The model was based on the assumption that spin diffusion is the main spin-lattice relaxation mechanism. The way that SSNMR relaxation time measurements could be used to characterize the polydispersity of crystalline powders using physical mixtures of dicumarol was also investigated. A short investigation of the effect of different compaction forces on the homogeneity of formulated tablets of salicylic acid was also conducted. Different 1H T1 times were obtained for salicylic acid at all compaction forces, and heavier compaction forces lead to a larger decrease in 1H T1 time. Finally, the effect of grinding on the chemical stability of a crystalline API gabapentin was investigated. Changes in 1H T1 times of ground crystalline gabapentin Form II were correlated with the chemical stability of the material: samples with shorter 1H T1 times were the least chemical stable. The physical meaning for the reduction in 1H T1 time observed was believed to be both the presence of crystal defects and the decrease in particle size of the material. This research provided evidence that SSNMR can be used to characterize bulk properties as well as molecular level characteristics of pharmaceutical solids. This could improve the characterization of formulated drug products during drug development.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Chemical stability
Particle size
Pharmaceutical solids
Relaxation times
Solid-state nmr
Correlation of solid-state NMR relaxation times to functional properties such as chemical stability and particle size
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/11468/1/Dempah_ku_0099D_12698_DATA_1.pdf
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Dempah_ku_0099D_12698_DATA_1.pdf
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Dempah_ku_0099D_12698_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/248322018-01-31T20:07:49Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Kalonia, Cavan Kumar
cmtemember
Middaugh, Charles R
cmtemember
Siahaan, Teruna J
cmtemember
Berkland, Cory J
cmtemember
Deeds, Eric J
2017-08-13T22:24:58Z
2017-08-13T22:24:58Z
2016-05-31
http://dissertations.umi.com/ku:14440
http://hdl.handle.net/1808/24832
The term protein aggregation is used in pharmaceutical biotechnology literature to describe a collection of different mechanisms that produce non-native, net irreversibly associated protein molecules. The presence of protein aggregates in therapeutic protein drugs is problematic because certain protein aggregates may induce an anti-drug immune response in patients. The work described in this Ph.D. thesis is focused on developing quantitative tools and theoretical models to better characterize and understand protein aggregation as a function of formulation conditions (solution pH, ionic strength, excipients, etc.) and external stresses (e.g., temperature, agitation, light, etc.). The methods developed here are then applied to develop a comprehensive understanding of the aggregation pathways of an IgG1 monoclonal antibody (mAb) under various conditions. Depending upon the protein itself, the formulation composition and the processing stress, protein aggregation may produce heterogeneous distribution of aggregates with different sizes and morphological properties. This work presents a novel data visualization method to monitor aggregate size, morphology, and concentration as a function of formulation variables such as solution composition, type of external stress, and stress duration. Such data visualization methods can be useful for isolating the effect of single variables. Another complementary method to determine the mass of subvisible particles (large aggregates with an equivalent spherical diameter of ~1-100 μm) was also developed in this work to better relate protein subvisible particle numbers to sample stability. Such calculation methods are often necessary because particle mass is often too low to be measured experimentally. When combined, these two methodologies serve as a set of powerful tools to better analyze protein aggregation because stressed samples with high particle numbers and small masses suggest that aggregate nucleation (monomers forming aggregate seeds) mechanisms are dominant. On the other hand, stressed protein samples with low particle numbers and large masses may point to aggregate growth mechanisms being dominant. Application of the data visualization and mass calculation methods to better characterize mAb aggregation led to a striking experimental observation that certain formulations could stabilize the IgG1 mAb against elevated temperatures but destabilize it against mechanical agitation. This, among other observations, led to the hypothesis that elevated temperatures promoted aggregation of this mAb in the bulk solution while mechanical agitation induced mAb particle formation at the air-solution interface. To better understand how formulation affected temperature induced aggregation of this mAb, kinetic models describing nucleation and growth processes were fit to mAb aggregation data collected at several incubation temperatures (25, 40 and 57 °C). The results of this study suggested that partially unfolded intermediates are an important driver of both aggregate nucleation and growth. Protein-protein interactions, on the other hand, only appeared to affect aggregate growth for this mAb. To further elucidate how mechanical agitation of mAb solutions could induce protein particle formation, controlled compression-expansion cycles were applied to the air water interface of mAb solutions. In this study, in collaboration with the Dhar laboratory, slow compression-expansion rates were found to induce aggregate formation at the air-solution interface. Faster compression-expansion rates appeared to disrupt the air-solution interface releasing protein particles into the bulk mAb solution. In addition, formulation composition was observed to affect the tendency of this IgG1 mAb to aggregate at the air-solution interface.
en
Copyright held by the author.
Pharmaceutical sciences
Colloidal Stability
Mechanism
Monoclonal Antibody
Protein Formulation
Proteing Aggregation
Subvisible Particles
Quantitative methods to elucidate and characterize various aggregation pathways of an IgG1 monoclonal antibody
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/24832/1/Kalonia_ku_0099D_14440_DATA_1.pdf
File
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Kalonia_ku_0099D_14440_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/24832/2/Kalonia_ku_0099D_14440_DATA_1.pdf.txt
File
MD5
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text/plain
Kalonia_ku_0099D_14440_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/295452020-07-09T21:46:36Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Wang, Michael Z
author
Doyle, Laura Michelle
cmtemember
Schoeneich, Christian
cmtemember
Stobaugh, John
cmtemember
Krise, Jeff
cmtemember
Zeng, Yong
2019-09-06T19:25:48Z
2019-09-06T19:25:48Z
2019-05-31
http://dissertations.umi.com/ku:16433
http://hdl.handle.net/1808/29545
Two main routes of drug elimination include renal excretion via the kidney and metabolic degradation via metabolizing enzymes (DMEs) in the liver, followed by renal excretion or biliary elimination of the now more polar molecule. Unlike renal excretion, liver metabolism tends to be highly variable between individuals due to various intrinsic and extrinsic factors such as age, genetics, smoking, and diet. The variability in liver DME activity among individuals creates a challenge in drug development and pharmacotherapy, especially for drugs that are required to be metabolized and have narrow therapeutic windows. If the liver DME activity of an individual could be predicted and each patient dosed according to their unique liver DME activity, the adverse effects or lack of effectiveness associated with these drugs may be prevented. Currently, two methods available for predicting an individual’s liver DME activity are genotyping and phenotyping. For genotyping, RT-PCR is used to determine the DNA sequence of the expressed enzyme. This reveals the specific polymorphism of the enzyme and the “typical activity” of the expressed polymorph is used to dose the patient accordingly. The issue with this however, is that it fails to account for other intrinsic or extrinsic factors that can affect the expression level of the given DME polymorph. On the other hand, phenotyping is done by administering a cocktail of drugs to a patient and monitoring the activity of the expressed enzyme(s). Because this reveals the true activity of the liver DMEs, it is more clinically relevant and used more often than genotyping. However, phenotyping is expensive and requires consistent monitoring by medical professionals in the hospital, thus is inconvenient. Accurate prediction of liver DME activity at the individual level in the clinical setting remains challenging, however if a more clinically friendly method were to be developed, it could lead to a broader range of potential drug candidates in drug development and lower risk of adverse drug responses. In this dissertation, the use of exosomes to act as biomarkers for liver DMEs is investigated. Exosomes are vesicles, typically 50 – 150 nm in diameter, secreted by cells into the extracellular space. In the human body, exosomal vesicles have been found in blood, saliva, urine, breast milk, and other bodily fluids. What makes exosomes unique from other vesicles secreted by cells, is that exosomes are formed by an endosomal route, thus contain cargo that reflecting the cell from which they are being secreted, in the extracellular space. This allows for the development of minimally invasive “liquid biopsies” to probe for markers of different diseases and cancers. While exosomes have been demonstrated as useful tools for diagnosis and monitoring patient response to treatment, they are yet to be used in the clinical setting. This is due to the lack of standardization in exosomal isolation and analysis. These challenges were also addressed in this dissertation. In summary, this dissertation describes the development of a liquid chromatography multiple-reaction-monitoring mass spectrometry (LC-MRM-MS) method for exosomal analysis and its benefits over more traditional assays. Following the method development, the presence of DMEs in exosomes were explored along with the ability of exosomal DME levels to be altered to reflect a change occurring in the secreting cell. Finally, the ability to isolate liver derived exosomes based on the expression of a liver specific marker protein, ASGR1, is explored. Further efforts of this project could lead to the development of a blood-based biopsy to evaluate the DME content of liver derived exosomes, which may correlate to liver DME activity, providing a new-found basis of personalized medicine.
en
Copyright held by the author.
Pharmaceutical sciences
ASGR-1
Drug Metabolizing Enzymes
Exosomes
LC-MRM-MS
Liver
Targeted Proteomics for Exosome Analysis and Its Application to Develop Blood Markers of Liver Drug-Metabolizing Enzymes
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29545/1/Doyle_ku_0099D_16433_DATA_1.pdf
File
MD5
100a4e5921047f1302cb22d81940266f
6975067
application/pdf
Doyle_ku_0099D_16433_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29545/2/Doyle_ku_0099D_16433_DATA_1.pdf.txt
File
MD5
cb9e2bc605e56b3e9485d8ec86a8dde6
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text/plain
Doyle_ku_0099D_16433_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216282020-10-16T14:36:36Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, Charles R
author
Thomas, Justin Cody
cmtemember
Laurence, Jennifer S
cmtemember
Siahaan, Teruna J
cmtemember
Volkin, David B
cmtemember
Karanicolas, John
2016-10-11T15:38:03Z
2016-10-11T15:38:03Z
2013-12-31
http://dissertations.umi.com/ku:13130
http://hdl.handle.net/1808/21628
To date, there is no approved antidote to treat or prevent the toxic effects of ricin exposure. RiVax, a recombinant ricin A chain subunit vaccine antigen, is one such antidote being developed as a prophylaxis. While it has been shown to be protective in numerous animal studies, RiVax is currently limited by its ability to elicit a robust toxin-neutralizing antibody (TNA) response. The underlying hypothesis of this dissertation is that a RiVax-based antigen with improved structural stability would result in an enhanced TNA response due to the preservation of conformationally-sensitive epitopes. To that end, two complimentary and orthogonal computational approaches were employed to design twelve point mutations predicted to stabilize the structure of RiVax. Differential scanning calorimetry across a range of pH values revealed seven of the twelve mutations were more stable than RiVax, two had essentially no effect, and three were destabilizing. Serological analysis of mice immunized with RiVax, one of two stabilized mutants, or one of two destabilized mutants suggested that the stabilized antigens induced a qualitatively better immune response. Eight double point mutants and a triple point mutant were then produced by combining the seven stabilizing mutations in various ways. Circular dichroism and fluorescence thermal unfolding curves showed that all nine derivatives were, to varying degrees, more stable than RiVax. Differential scanning calorimetry (DSC) detected two distinct transitions - one which was rather dramatically affected by the mutations and a second which showed more meager gains in stability more in line with the spectroscopic techniques. The first transition was speculated to arise from changes to the rather unstable C-terminal region of RiVax. Serological analysis of mice immunized with RiVax or one of four multi-site derivatives (selected on the basis of highest Tm,1 from DSC analysis) showed that three of the derivatives elicited a more rapid and statistically superior TNA response relative to RiVax. When the mouse study was repeated with a lower antigen dose, a RiVax derivative containing mutations V81I, C171L, and V204I was clearly superior to RiVax and the other three derivatives at eliciting TNA. Furthermore, pepscan analysis suggested that the improvement in TNA was due to preservation of conformationally-sensitive, neutralizing epitopes because reactivity differences with the overlapping peptides did not adequately explain the dramatic improvement in TNA elicited by the abovementioned triple mutant. Due to the results presented in this dissertation, the RiVax triple mutant warrants further development as a ricin vaccine candidate.
en
Copyright held by the author.
Pharmaceutical sciences
antibodies
antigen
mutagenesis
protein stability
ricin toxin
vaccines
Toward the Development of an Improved Ricin Vaccine
Dissertation
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Thomas_ku_0099D_13130_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/295522019-11-05T23:51:42Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Yang, Yi
cmtemember
Stobaugh, John
cmtemember
Volkin, David
cmtemember
Siahaan, Teruna
cmtemember
Desaire, Heather
cmtemember
Gennaro, Lynn
2019-09-06T19:42:26Z
2019-09-06T19:42:26Z
2019-05-31
http://dissertations.umi.com/ku:16489
http://hdl.handle.net/1808/29552
In the pharmaceutical industry, recombinant monoclonal antibodies (mAbs) have become a major focus of therapeutic drug development due to their broad applications in many disease areas. During manufacturing and storage of mAb drug products, metal-catalyzed carbonylation, a post-translational modification referring to the formation of carbonyls (aldehydes and ketones) on proteins after metal-catalyzed oxidation, is a relevant product variant of mAbs, which may impact mAb safety and/or efficacy. However, to date, very little is known about the occurrence of metal-catalyzed carbonylation during mAb manufacturing and storage or the effects of metal-catalyzed carbonylation on chemical and physical stability of mAbs. To answer those questions, this dissertation first focused on developing a new protein carbonylation assay with improved assay precision and robustness over the conventional assays. Using the new protein carbonylation assay, a study was performed to investigate various cell culture and formulation factors, which revealed that iron ion, hydrogen peroxide, and polysorbate 20 can critically impact mAb carbonylation during manufacturing or storage. This study also revealed that metal-catalyzed carbonylation positively correlated with increased acidic charge heterogeneity and aggregation propensity of mAbs. To elucidate the increased acidic charge heterogeneity, the acidic fraction of a model IgG1 mAb after metal-catalyzed oxidation was collected and characterized, which showed that metal-catalyzed carbonylation products (primarily threonine carbonylation products) directly contributed to the increased acidic charge heterogeneity. Several additional oxidation products, such as carboxylic acids (from further oxidation of aldehydes) and pyroglutamate (from oxidation of proline residues in the hinge region), were identified for the first time in mAbs, which provides further explanation to the increased acidic charge heterogeneity. To elucidate the increased aggregation propensity, this dissertation used a model stress system and anions from the Hofmeister series to investigate the effects of metal-catalyzed carbonylation on physical stability of the model IgG1 mAb. In particular, the investigation applied a site-specific carbonylation analysis, which revealed for the first time that mAb aggregation can be affected by carbonylation location, carbonylation type, and buffer type. These findings showed that effects of metal-catalyzed carbonylation on physical instability of mAbs can be much more complex than what have been previously proposed/suggested in the literature. Finally, this dissertation investigated formation of Schiff base crosslinks as a potential route of chemical instability of the metal-catalyzed carbonylation products. To facilitate the investigation, a new analytical methodology was developed to characterize crosslinked peptides. This new methodology addressed several key analytical challenges for crosslink analysis and successfully identified bissulfosuccinimidyl suberate (BS3)-crosslinked peptides in a BS3-treated mAb sample. Using the new analytical methodology, this study showed that Schiff base formation is a not major degradation pathway of mAbs even under a harsh condition by copper-catalyzed oxidation. In summary, this dissertation provided a comprehensive understanding of the chemical and physical instability of mAbs induced by metal-catalyzed carbonylation, which can help improve mAb stability against metal-catalyzed carbonylation in the future.
en
Copyright held by the author.
Pharmaceutical sciences
critical quality attributes
metal catalyzed oxidation
oxidative carbonylation
post-translational modification
protein stability
recombinant monoclonal antibody
Chemical and Physical Instability of Monoclonal Antibodies Induced by Metal-catalyzed Carbonylation
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29552/1/Yang_ku_0099D_16489_DATA_1.pdf
File
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Yang_ku_0099D_16489_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29552/2/Yang_ku_0099D_16489_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/43332020-06-26T18:44:33Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Hong, Sung Jung
cmtemember
Audus, Kenneth L.
cmtemember
Michaelis, Elias K.
cmtemember
Stobaugh, John F.
cmtemember
Krise, Jeffrey P.
2009-02-02T05:47:44Z
2009-02-02T05:47:44Z
2008-08-28
http://dissertations2.umi.com/ku:2708
http://hdl.handle.net/1808/4333
Protein post-translational modifications are of great interest due to their effects on protein structure and function. Our interest lays in the nitration of tyrosine residues by powerful oxidants such as peroxynitrite (ONOO-) forming 3-nitrotyrosine. The post-translational modification of tyrosine to 3-nitrotyrosine is a hallmark for protein oxidation. Traditional proteomics methods employed for the detection of nitrated peptides include SDS-PAGE, 2D-gel electrophoresis, Western blot, as well as immunoprecipitation. These are good and well accepted separation and detection methods, however they are only qualitative and don't tell us information about the specific sites of nitration. To overcome the drawbacks of these traditional proteomics methods, we have employed different methods that allowed us to perform all analytical steps in-solution. Also, we have explored the application of a novel 3-nitrotyrosine specific fluorescent, isotopic labeling technique developed in our labs for the sensitive detection and quantitation of 3-nitrotyrosine in different types of biological samples.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
A Proteomic Study of Protein Tyrosine Nitration
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/4333/1/umi-ku-2708_1.pdf
File
MD5
f625a5b9125fa62e1c6af35c0431dd43
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umi-ku-2708_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/4333/2/umi-ku-2708_1.pdf.txt
File
MD5
73edd9b72b6b222a4998b763952af934
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umi-ku-2708_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/42422020-07-16T15:32:06Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Topp, Elizabeth M
author
Sinha, Sandipan
cmtemember
Siahaan, Teruna J.
cmtemember
Munson, Eric J.
cmtemember
Lunte, Susan M.
cmtemember
Camarda, Kyle
2008-09-29T05:38:57Z
2008-09-29T05:38:57Z
2008-06-16
http://dissertations.umi.com/ku:2594
http://hdl.handle.net/1808/4242
The chemical and physical stability of proteins in solution and solids was addressed in this dissertation. Protein-excipient interactions in lyophilized solids were studied by hydrogen/deuterium exchange with mass spectrometry (chapter 3) while glycosylation quanitification (chapter 4) and deamidation (chapter 5) was characterized in antibodies in solution. LC/ESI-MS was the method of choice for all studies. Hydrogen/deuterium exchange study showed that the method can be used to obtain region specific information about protein-excipient interactions in solids. It was demonstrated that exchange protection did not occur uniformly along the backbone of the protein and was dependant on excipient type and protein structure. The glycosylation quanitification study demonstrated that the Fc/2 (limited proteolysis followed by reduction) method was relatively quick and accurate and showed comparable values to the standard sugar release assay. Antibody deamidation study demonstrated that secondary structure played a pivotal role in determination of the deamidation products in antibodies.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Chemical and Physical Characterization of Therapeutic Proteins in Solution and Amorphous Solids
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/4242/1/umi-ku-2594_1.pdf
File
MD5
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2386221
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umi-ku-2594_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/4242/2/umi-ku-2594_1.pdf.txt
File
MD5
ad39310402f91c0fa5ab3ec5565d58c8
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umi-ku-2594_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253632018-07-23T16:43:09Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Arora, Jayant
cmtemember
Weis, David D
cmtemember
Middaugh, C. Russell
cmtemember
Siahaan, Teruna J
cmtemember
De Guzman, Roberto N
2017-11-16T03:00:31Z
2017-11-16T03:00:31Z
2016-08-31
http://dissertations.umi.com/ku:14855
http://hdl.handle.net/1808/25363
https://orcid.org/0000-0002-9600-2232
Immunoglobulin G1 monoclonal antibodies (IgG1-mAbs) are one of the most important and fastest growing class of biotherapeutic agents. These mAbs are being used to treat a wide range of medical conditions such as cancer, macular degeneration, autoimmune diseases, rheumatoid arthritis, etc. Antibodies are dynamic molecules and their dynamic nature governs their physiological and biological functions. Antibodies are protein based drugs and are prone to both physical and chemical degradation in vitro. The biggest concerns related to IgGs mAb stability is their propensity to form protein aggregates (at low and high protein concentrations) and transient protein-protein interactions at high protein concentrations leading to dramatic increase in solution viscosity. Predicting protein stability and mapping protein interactions at high protein concentrations remains some of the most desirable long term goals of protein formulation development. This dissertation’s second chapter focused on exploring the utility of hydrogen exchange mass spectrometry (HX-MS) in predicting stability profile of an IgG1 mAb, mAb-4, upon addition of various destabilizing phenolic antimicrobial preservatives (APs). The trends in mAb-4’s physical stability measurements using differential scanning calorimetry and extrinsic fluorescence spectroscopy (thermal stability) and size exclusion chromatography (aggregation propensity) showed correlations with significant increases in local flexibility of the aggregation hot-spot peptide segment in the CH2 domain of mAb-J (HC 237-254) upon addition of APs. Most hydrophobic AP (m-cresol) caused the greatest decrease in physical stability of mAb-4 and also the biggest increase in the local flexibility of CH2 domain peptide hot-spot of the antibody. Global deuterium uptake by mAb-4 was also highest in the presence of m-cresol, followed by phenol, phenoxyethanol and benzyl alcohol. In the third and fourth chapter, the effect of different solution and environmental variables on viscoelastic behavior and propensity of concentration-dependent self-association of two IgG1 mAbs was tested. One of the IgG1 mAbs, mAb-C showed a primarily hydrophobic interaction driven protein association behavior, however, the other IgG1 mAb, mAb-J, showed a distinct association mechanism where the antibody monomers associated through electrostatic attractive interactions. A novel HX-MS methodology was developed to map protein-protein interaction interfaces of transient intermolecular antibody associations at high protein concentrations. Antibody solutions of low (non-associating) and high protein concentrations (associating) were lyophilized and reconstituted directly in D2O solutions to initiate HX process directly at target concentrations. Protein interface of mAb-C reversible self-association was confined in the relatively hydrophobic VH and VL domains of the antibody that spanned its CDR2H and CDR2L loops, indicating towards a Fab-Fab interaction drive association event. HX-MS also revealed distant dynamic coupling effects of mAb-C association in the form of significant increases in local flexibility of certain peptide segments in the VH and CH2 domains of the antibody. HX-MS analysis of mAb-J reversible self-association revealed one of the interfaces in the VH and VL domain (positively charged, spanning CDR3H and CDR2L) and other interface in the CH3 domain of the antibody (negatively charged). Hence, HX-MS can provide a robust solution to protein physical stability prediction for rational design of protein formulation strategies and high-resolution protein-protein interaction interface mapping at high protein concentrations for engineering mutant antibody molecules with superior physiochemical properties and enhanced stability.
en
Copyright held by the author.
Pharmaceutical sciences
High protein concentration
Hydrogen exchange mass spectrometry
Monoclonal antibodies
Protein aggregation
Protein-protein interactions
Reversible self-association
Towards a greater mechanistic understanding of reversible protein-protein interactions and irreversible aggregation of IgG1 monoclonal antibodies
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25363/1/Arora_ku_0099D_14855_DATA_1.pdf
File
MD5
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Arora_ku_0099D_14855_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25363/2/Arora_ku_0099D_14855_DATA_1.pdf.txt
File
MD5
be1305285576f4f7d62abc3609290ec8
348117
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Arora_ku_0099D_14855_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216412018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Siahaan, Teruna J
author
Farokhi, Elinaz
cmtemember
Tolbert, Thomas
cmtemember
wang, Zhuo W
2016-10-11T16:50:23Z
2016-10-11T16:50:23Z
2014-05-31
http://dissertations.umi.com/ku:13470
http://hdl.handle.net/1808/21641
The objective of this work is to evaluate the binding mechanisms of synthetic cadherin peptides (ADTC7, ADTC9 and cHAVc3) to the EC1 domain of human E-cadherin. The binding sites of these peptides to the EC1 domain were determined by titrating the 15N-labeled EC1 domain with each peptide. The changes in the 1H,15N-HSQC NMR spectra were observed upon peptide titration. The AutoDock Vina molecular modeling program was also used to predict the binding sites of each cadherin peptide on the EC1 domain. NMR data confirmed that there are three potential binding sites of ADTC7 on the EC1 domain; these binding sites are around residues I53/V48, D103, and G115. The two potential binding sites of ADTC9 peptide are around I4 and I53/V48 residues of EC1. The NMR data showed that ADTC7 peptide has higher binding affinity to the EC1 domain than ADTC9 peptide. For cHAVc3, it binds selectively to at the D103 residue on EC1. AutoDock Vina studies confirm some of the binding sites found by NMR studies. In the future, a more detail study will be conducted to evaluate the effect of peptide binding on the dynamics properties of the EC1 domain.
en
Copyright held by the author.
Pharmaceutical sciences
Determination of Binding Sites of Cadherin Peptides on the EC1 domain of E-cadherin using NMR Spectroscopy
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21641/1/Farokhi_ku_0099M_13470_DATA_1.pdf
File
MD5
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Farokhi_ku_0099M_13470_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21641/2/Farokhi_ku_0099M_13470_DATA_1.pdf.txt
File
MD5
b0893c7f59ea7a2fe96c54bf64724b8c
40180
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Farokhi_ku_0099M_13470_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/97312020-08-25T14:11:22Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Siahaan, Teruna J.
author
Buyuktimkin, Barlas
cmtemember
Berkland, Cory J.
cmtemember
Laurence, Jennifer S.
cmtemember
Volkin, David B.
cmtemember
Kuczera, Krzysztof
2012-06-03T14:24:52Z
2012-06-03T14:24:52Z
2011-12-31
http://dissertations.umi.com/ku:11810
http://hdl.handle.net/1808/9731
Peptides and proteins have been used as carriers to target and deliver molecules to sites of action. Conjugating a drug to a macromolecule offers the unique advantage of being able to target drug to a specific cell surface receptor with high affinity, thereby increasing efficacy and reducing side effects. Furthermore, conjugations between two different peptides, or between peptide and protein, that have activities to modulate two receptors have shown promising results in suppressing autoimmune diseases in animal models. Therefore, the objective of the dissertation was to explore the possibility of selectively targeting peptide and protein conjugates to antigen presenting cells to suppress autoimmune diseases. The I-domain of leukocyte function associated antigen-1 (LFA-1) conjugated to antigenic PLP139-151 peptide (IDAC-3) suppressed experimental autoimmune encephalomyelitis (EAE) when delivered in a vaccine-like manner by shifting the immune balance away from Th17-mediated pathology by increasing involvement of T-reg cells (Chapter 2). PLP139-151 conjugated to LABL adhesion peptide (Ac-PLP-BPI-NH2-2) was formulated in a colloidal gel for a one-time subcutaneous administration to suppress EAE. A vaccine-like administration of the peptide conjugate suppressed EAE as well as the relapse. In vitro cytokine studies suggested that the mechanism of suppression was due to the shift of the immune balance away from a Th17-mediated response (Chapter 3). The utility of BPI to target other autoimmune diseases such as collagen-induced arthritis (CIA) was also investigated. Here, collagen type II peptides were conjugated to LABL (CII-BPI). It was found that suppression of disease is dependent upon the sequence of the antigen, and that the mechanism of disease suppression was linked to a shift in the immune balance from a proinflammatory to a regulatory response (Chapter 4).
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Utilizing Antigenic Peptide and Adhesion Molecule Conjugates to Suppress Autoimmune Disease in Animal Models
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/9731/1/Buyuktimkin_ku_0099D_11810_DATA_1.pdf
File
MD5
98b9b665b38e70bf12a8be53c4309a77
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Buyuktimkin_ku_0099D_11810_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/9731/2/Buyuktimkin_ku_0099D_11810_DATA_1.pdf.txt
File
MD5
0df8a223c0e3cb85f156e23c154a5ef9
183240
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Buyuktimkin_ku_0099D_11810_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/76322020-08-07T12:56:53Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Laurence, Jennifer S.
advisor
Krishnan, Sampath
author
Park, Jihea
cmtemember
Volkin, David B.
2011-06-21T16:04:18Z
2011-06-21T16:04:18Z
2011-01-31
http://dissertations.umi.com/ku:11293
http://hdl.handle.net/1808/7632
Purpose: The purpose of this study is to investigate the effect of pH and potential stabilizers on structure and long-term stability of an IgG1 monoclonal antibody in the solid state after freeze-drying. The inter-relationships between preservation of secondary and tertiary structure of the protein in the solid state and long term storage stability under different formulation conditions and temperatures was obtained from examining data collected using spectroscopic techniques and stability-indicating assays, respectively. Methods: Anti-Streptavidin IgG1 antibody was formulated with mannitol at pH 3.0, 5.0 and 7.0 in the presence and absence of sucrose as a stabilizer. All samples were stored at 4 ºC, 25 ºC, and 37 ºC up to 12 months and at 50 ºC for 6 months. Physical degradation of each lyophilized formulation was monitored using size-exclusion chromatography (SEC), covalent degradation was monitored using cation-exchange chromatography (CEX), and sub-visible particle counts (SbVP) were measured by HIAC. The secondary structure of the protein in the solid state was characterized using Fourier transform infrared (FTIR) spectroscopy and tertiary structure was monitored using fluorescence spectroscopy. Raman spectroscopy was also used to determine changes in secondary and tertiary structure spectral features. Results: The IgG1 antibody underwent significant secondary structural perturbations at pH 3.0 regardless of excipients, and all formulations without sucrose also showed decreased structural stability in the solid state. Based on observation of structural changes, formulation at pH 5.0, showed the least change over time and at elevated temperatures. This correlated with long-term stability upon reconstitution with respect to protein aggregate formation and sub-visible particle counts. Conclusions: The results of the study show that protein secondary and tertiary structural preservation in the solid state correlates to improved long-term stability of the monoclonal antibody in the different lyophilized formulations.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Effect of pH, sucrose and mannitol on structure and long-term stability of a model IgG1 antibody upon freeze-drying
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/7632/1/Park_ku_0099M_11293_DATA_1.pdf
File
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e12a33b3d7f774fc9ba06e3455fb408a
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Park_ku_0099M_11293_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/7632/2/Park_ku_0099M_11293_DATA_1.pdf.txt
File
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a9e292e3a634e7afd098d47a169af152
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Park_ku_0099M_11293_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/295512021-10-28T19:39:03Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Tolbert, Thomas J
author
White, Derek Robert
cmtemember
Siahaan, Teruna J
cmtemember
Volkin, David B
cmtemember
Stobaugh, John F
cmtemember
Weis, David D
2019-09-06T19:40:06Z
2019-09-06T19:40:06Z
2019-05-31
http://dissertations.umi.com/ku:16408
http://hdl.handle.net/1808/29551
Antibody-based therapeutics are a rapidly expanding class of biopharmaceuticals. The number of approved antibody-based therapeutics by the FDA and EMA has more than doubled in the last five years, and they are expanding into areas such as antibody-drug conjugates, Fc fusions, bispecific antibodies, and biosimilars. Most antibody-based therapeutics use the Immunoglobulin isotype G subclass 1 (IgG1) antibody. Some IgG1-based therapeutics obtain their therapeutic efficacy by modulating the immune system for the treatment of several disease-types including cancer, autoimmune disease, and organ transplant rejection. This work further explores our understanding of IgG1-mediated immunomodulation by utilizing the fragment crystallizable (Fc) region of IgG1 in three research projects. In the first project, an IgG1 Fc fusion was prepared as a potential treatment for multiple sclerosis, an autoimmune disease that affects 2.3 million people worldwide. This disease involves immune system attack and destruction of the myelin protein surrounding the neurons in the central nervous system. One promising class of compounds that selectively prevent the activation of immune cells involved in the destruction of myelin are Bifunctional Peptide Inhibitors (BPIs). In an effort to further improve the bioactivity of BPIs, the BPI peptides were conjugated to the termini of IgG1 Fc to prepare a BPI-Fc fusion. This fusion was tested in a mouse model of multiple sclerosis. Compared to the PBS-treated control, mice treated with the BPI-Fc fusion showed significantly reduced disease symptoms, did not experience weight loss, and showed reduced demyelination. These results demonstrated that the BPI peptides were highly active at suppressing the disease when prepared as an Fc fusion. In the second project, the N-glycosylation of IgG1 Fc was modified. The N-glycosylation of IgG1 can markedly affect its function, stability, pharmacokinetics, solubility, and immunogenicity. However, recombinant expression of IgG1 results in a mixture of N-glycoforms. This heterogeneity makes it difficult to understand how N-glycosylation affects IgG1 because different N-glycoforms can affect the antibody differently. To solve this problem, this work utilized IgG1 Fc as a model system to prepare homogenous IgG1 Fc N-glycoforms, and their effects on IgG1 Fc were studied individually. In-vitro enzymatic synthesis was used to prepare homogenous oligomannose, hybrid, and complex N-glycoforms. The effect of each non-fucosylated N-glycoform on IgG1 Fc stability was compared using differential scanning calorimetry. The results showed that the complex N-glycoform was more stable than the hybrid and oligomannose N-glycoforms. Additionally, the effect of each N-glycoform on IgG1 Fc function was compared in an in-vitro receptor-binding assay using FcγRIIIa, the receptor involved in activating Antibody-dependent Cellular Cytotoxicity (ADCC). Results showed that the binding affinity increased with increased N-glycan processing. Lastly, the hybrid and complex IgG1 Fc N-glycoforms were compared for their abilities to accept core-linked fucose. Results showed that the complex N-glycoform accepted fucose much more slowly compared to the hybrid N-glycoforms. In the third project, IgG1 Fc was assembled as a protein-polymer conjugate in order to increase its valency. Multivalent display of IgG1 is necessary in order to obtain an avidity effect strong enough to activate immune system effector functions, such as ADCC. IgG1 Fc-polymer conjugate was prepared using controlled polymerization to first synthesize a water soluble, linear poly(acrylamide-peptide) co-polymer. This co-polymer was then used as a scaffold onto which multiple IgG1 Fc proteins were site-specifically ligated. The IgG1 Fc-polymer conjugate was compared against IgG1 Fc in a receptor binding assay with FcγRIIIa. The results showed that the IgG1 Fc-polymer conjugate bound FcγRIIIa 800 times stronger compared to free IgG1 Fc. This large increase in binding strength was caused by the multimer having a much slower dissociation rate. The research presented in this dissertation improves our fundamental understanding IgG1-mediated immunomodulation and may also help in the development of improved antibody- based therapeutics.
en
Copyright held by the author.
Pharmaceutical sciences
Antibody
Fc fusion
Fucosylation
Glycosylation
Site-specific
Sortase
Utilizing IgG1 Fc As An Immunomodulator
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/29551/1/White_ku_0099D_16408_DATA_1.pdf
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White_ku_0099D_16408_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/29551/2/White_ku_0099D_16408_DATA_1.pdf.txt
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MD5
8c83a1b80a99c6690b8878b0c599a2dd
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White_ku_0099D_16408_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/106912018-01-31T20:08:01Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Laurence, Jennifer S.
author
Nelson, Benjamin Nels
cmtemember
Munson, Eric J.
cmtemember
Stobaugh, John F.
cmtemember
Berkland, Cory J.
cmtemember
Lunte, Susan M.
cmtemember
Carlson, Robert G.
2013-01-20T17:52:23Z
2013-01-20T17:52:23Z
2011-12-31
http://dissertations.umi.com/ku:12074
http://hdl.handle.net/1808/10691
Solid-state NMR spectroscopy (ssNMR) is an extremely powerful technique for the analysis of pharmaceutical dosage forms. A major limitation of ssNMR is the number of samples that can be analyzed in a given period of time. Development of three versions of probes that contain multiple magic angle spinning (MAS) modules for interleaved acquisition has been done, and each shows no loss in spectral quality compared to a standard probe. A prototype probe incorporating two MAS modules was first developed. This version is limited to being a two-module probe due to the large amounts of space required for the tuning elements, which are located next to the MAS modules. A new probe design incorporating coaxial transmission lines and smaller MAS modules has also been constructed. This probe allows for close proximity of the MAS modules (within 3 cm) and the capability of remote tuning and sample changing. This probe design can be easily scaled to incorporate more than two MAS modules, which is a limitation of the previous design. The number of modules that can be incorporated is only limited by the number of transmission lines that will fit in a cross-sectional diameter of the bore and the axial field length of the magnet. A third version addresses the main issues of length and linear actuation that the first generation probes have. So that the superconducting magnet can be left at "factory" height, a non-actuated probe that has the ability to collect two samples at a time has been constructed and tested. The radio frequency circuits have been isolated to such a degree that they do not dramatically affect the spectra of one another. Spectra of ssNMR standards: methylglutaric acid, hexamethylbenzene, and adamantane were acquired to show comparable performance of all multiple sample probe versions and conventional probes.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Aspirin
Hmb
Ibuprofen
Mga
Probe
SSNMR
DEVELOPMENT OF MULTIPLE SAMPLE SOLID-STATE NMR PROBES FOR ANALYSIS OF PHARMACEUTICAL COMPOUNDS AND FORMULATIONS
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10691/1/Nelson_ku_0099D_12074_DATA_1.pdf
File
MD5
19bc2b30f055b4e4f6807c5e1dba099e
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Nelson_ku_0099D_12074_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10691/2/Nelson_ku_0099D_12074_DATA_1.pdf.txt
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92850
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Nelson_ku_0099D_12074_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216572018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stella, Valentino J
author
Liao, Salina Chi-Man
cmtemember
Stobaugh, John
cmtemember
Strickley, Robert
2016-10-11T19:05:55Z
2016-10-11T19:05:55Z
2016-05-31
http://dissertations.umi.com/ku:14444
http://hdl.handle.net/1808/21657
Supersaturation of four structurally related crystalline carboxylic acid drugs (naproxen, indomethacin, ibuprofen, and etodolac) was studied in aqueous acidic conditions at 37ºC in the absence and presence of pre-dissolved HPMC. A solvent-shift method was used in which drug-containing DMSO solution concentrates were prepared with each molecule and carefully added to aqueous acidic solutions while stirring. Tests were performed to measure drug dissolved concentration as a function of time and to characterize any resulting precipitate. Supersaturation was observed for all four model carboxylic acid drugs in the presence of HPMC-containing aqueous acidic solutions. When precipitation occurred the isolated solid drug was characterized and shown to increase in amorphous character or produce completely amorphous solid. The solution and solid-state data suggests that the mechanisms by which HPMC induces supersaturation include both increased equilibrium solubility and crystallization inhibition in the presence of HPMC in naproxen, indomethacin, and ibuprofen. In etodolac, there was no observed significant increase of equilibrium solubility, and only a loss of crysallinity upon precipitation in kinetic solubility studies. Additional studies with etodolac showed that the grade and viscosity of HPMC did not significantly affect the degree of supersaturation maintained. However, an increased initial degree of supersaturation of etodolac results in a decreased onset time of precipitation. Within the range studied the optimal degree of supersaturation of etodolac was 5 in which no precipitation occurred, at a degree of supersaturation of 7 precipitation occurred after 3 hours, whereas at a degree of supersaturation of 10 precipitation occurred immediately. The studies suggest that the solubilizing and supersaturating-promoting effects of HPMC may be useful in designing preclinical, clinical and commercial formulations and drug products to potentially improve the oral bioavailability of poorly water-soluble compounds.
en
Copyright held by the author.
Pharmaceutical sciences
HPMC
Precipitation inhibition
Supersaturation
Induced Supersaturation by Hydroxypropylmethyl Cellulose Under Aqueous Acidic Conditions of a Series of Carboxylic Acid Drugs
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21657/1/Liao_ku_0099M_14444_DATA_1.pdf
File
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Liao_ku_0099M_14444_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21657/2/Liao_ku_0099M_14444_DATA_1.pdf.txt
File
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d0f178645d56ce25e211a1caac790a21
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Liao_ku_0099M_14444_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/81372020-08-10T14:46:57Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory J.
author
Khondee, Supang
cmtemember
Middaugh, C. Russell
cmtemember
Siahaan, Teruna J.
cmtemember
Forrest, Laird
cmtemember
Dhar, Prajna
2011-10-09T01:25:29Z
2011-10-09T01:25:29Z
2011-05-31
http://dissertations.umi.com/ku:11419
http://hdl.handle.net/1808/8137
Polyelectrolytes have emerged as a versatile, simple and promising tool to deliver therapeutic payloads. Their ability to form complexes with oppositely charged polymers or biomacromolecules has led to various applications in the pharmaceutical and biotechnology industries. In this thesis, three different polyelectrolyte delivery systems have been developed and explored for potential uses in gene and protein delivery. Polyvinylamine (PVAm) nanogels with different amounts of surface charge and degradability were used to systematically inspect gene transfection efficiency and cytotoxicity. Transfection efficiency of non-degradable nanogels increased with increasing amounts of positive charge. Intriguingly, acid-labile nanogels bearing low charge showed sustained gene transfection and low cytotoxicity. An intricate balance between transfection efficiency and cytotoxicity is crucial for gene vectors. These results led to an exploration of less toxic, small polycations. Historically, polyplexes using small polycationic peptides such as TAT have shown relatively poor gene transfection, however, previous studies in our group showed that the transfection efficiency could be enhanced by condensing these large polyplexes using calcium. In this thesis, the LABL peptide targeting intercellular cell-adhesion molecule-1 (ICAM-1) was conjugated to TAT peptide using a polyethylene glycol (PEG) spacer. Though the transfection efficiency of TAT polyplexes was reduced by PEGylation, TAT complexes targeting ICAM-1 were able to restore high levels of gene transfection. Thus, targeted TAT polyplexes offer promise for gene delivery to sites of injury or inflammation. Next, other PEGylation strategies using polyelectrolytes were explored. Repifermin, a truncated version of fibroblast growth factor-10 (FGF-10) also known as keratinocyte growth factor-2 (KGF-2), is a heparin-binding protein with potent regenerative properties. The protein unfolds and aggregates at relatively low temperature (~37 oC). The thermal stability of several FGFs was enhanced by electrostatic interactions with polyanions. PEG was grafted to the polyanions pentosan polysulfate (PPS) and dextran sulfate (DS). The potential uses of polyanion conjugates were explored using a variety of spectroscopic and calorimetric methods, and dynamic light scattering. PPS-PEG and DS-PEG conjugates were able to stabilize KGF-2 by increasing the melting temperature of the protein complexes. Though there are several parameters that could be optimized to improve the protein structure upon binding, polyanion-PEG conjugates, however, are encouraging reagents that can improve the thermal stability of heparin-binding proteins via electrostatic PEGylation.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Gene delivery
Nanoparticles
Polyelectrolyte
Protein delivery
Polyelectrolyte-based Nanoparticles for Gene and Protein Delivery
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/8137/1/Khondee_ku_0099D_11419_DATA_1.pdf
File
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Khondee_ku_0099D_11419_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/8137/2/Khondee_ku_0099D_11419_DATA_1.pdf.txt
File
MD5
e0b70724772eadecb0a79b0356b3b43e
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Khondee_ku_0099D_11419_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216512018-11-01T18:09:01Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Laird
author
Yang, Qiuhong
cmtemember
Krise, Jeff
cmtemember
Siahaan, Teruna J.
cmtemember
Tolbert, Thomas
cmtemember
Ren, Shenqiang
2016-10-11T17:22:00Z
2016-10-11T17:22:00Z
2014-12-31
http://dissertations.umi.com/ku:13782
http://hdl.handle.net/1808/21651
https://orcid.org/0000-0001-7658-1647
Clinical outcomes of conventional anticancer therapies are often compromised due to off-target toxicity and adaptive drug resistance. Moreover, currently there are no imaging modalities that can be utilized for real-time monitoring of therapeutic responses in the human body. Therefore, there is a critical need to develop a novel generation of personalized medicine that combines functionalities of diagnosis and therapy, with an ultimate goal of early detection, accurate treatment and timely assessment of therapeutic efficacy. Over the last few decades, a variety of nano-medical materials or devices such as liposomes, micelles, quantum dots, magnetic nanoparticles and plasmonic nanobubbles have been developed to deliver therapeutic products or diagnostic agents to the sites of disease in a controlled manner with reduced or eliminated side effects to normal tissues. This dissertation focuses on the development of functional molecular imaging probe and nanoparticles-based therapeutic agent delivery systems for effective theranostics of lymphatically metastatic cancer, thus opening new avenues to combat cancer. In chapter 2, a near-infrared (NIR) absorbing dye -based caspase-9 image probe was synthesized in 11 steps to directly detect apoptotic cells with high specificity. This cell-permeable molecular contrast agent has demonstrated the feasibility of monitoring cancer cell apoptosis induced by chemotherapeutics in mice bearing head and neck squamous cell carcinoma (HNSCC), via non-invasive photoacoustic imaging (PAI) within 24 h after treatment, thus to predict treatment efficacy. In chapter 3, a biocompatible core/shell FePt@Fe3O4 magnetic nanoparticles (MNPs) was developed as a robust probe for magnetic resonance imaging (MRI) and to mediate hyperthermia treatment against breast tumor. Enhanced anti-tumor effectiveness was demonstrated in a mouse model of 4T1.2 Neu breast tumor as a consequence of the high magnetic-thermal energy transfer capability of MNPs. In addition, increased MRI contrast in the tumor region potentiated the clinical application of MNPs for cancer diagnosis. In chapter 4, Cabozantinib (XL-184), a poorly water-soluble pan-kinase inhibitor, was encapsulated into a DSPE-PEG2000 micellar formulation with excellent colloidal stability. Compared with the free XL-184 solution, drug-loaded micelles exhibited increased intracellular drug uptake and higher cytotoxicity in one human lung adenocarcinoma epithelial cell line and two human malignant glioblastoma cell lines. In chapter 5, a high molecular-weight hyaluronic acid-deferoxamine (DFO) conjugated was synthesized for sustained release delivery of DFO, whose potent iron-chelating capability can be utilized to reverse the radiotherapy-induced pathologic effects. The HA-DFO conjugate exhibited significantly decreased cytotoxicity to normal cells and excellent biodegradability. In addition, localized HA- DFO injection stimulated vascularity and improved bony regeneration and union after radiotherapy. In chapter 6, a nano-hyaluronic acid (HA)-based anticancer drug, HA- Cisplatin, was subcutaneously injected in an in-vivo murine model for locally advanced melanoma. Compared with the untreated control group and cisplatin- treated group (intravenous or subcutaneous injection), significant tumor shrinkage was observed in the subcutaneous peri-tumoral HA-cisplatin group, offering great potential as a therapeutic option in the treatment of certain types of human melanoma.
en
Copyright held by the author.
Pharmaceutical sciences
Anticancer
Hyperthermia
Lymphatic
Nanomaterials
Nanoparticles
Theranostics
Development of theranostics nanomaterials
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21651/1/Yang_ku_0099D_13782_DATA_1.pdf
File
MD5
59c22eaf6bd44b6c99aff992b2be0e70
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Yang_ku_0099D_13782_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21651/2/Yang_ku_0099D_13782_DATA_1.pdf.txt
File
MD5
064bd96a8726dc683cef369f8b2731c4
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Yang_ku_0099D_13782_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/248312018-01-31T20:07:48Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Bane, Jessica Mae
cmtemember
Volkin, David B
cmtemember
Wang, Michael
cmtemember
Siahaan, Teruna J
cmtemember
Desaire, Heather
2017-08-13T22:23:53Z
2017-08-13T22:23:53Z
2015-05-31
http://dissertations.umi.com/ku:13862
http://hdl.handle.net/1808/24831
Protein pharmaceuticals, like monoclonal antibodies (mAbs), are sensitive to many degradation pathways, such as oxidation and photodegradation. Photostability testing provides essential information to characterize protein stability because mAbs are exposed to light during the production and storage process, which could lead to instability problems. Photostability testing has also become increasingly important to demonstrate likeness between biosimilars and original protein therapeutics. All amino acids are sensitive to oxidation, but only the aromatic amino acids and the disulfide bond are directly sensitive to light. The Trp residue is the most sensitive to light, and its photochemistry has been studied extensively, but the photochemistry involving both Trp and the disulfide bond in peptides and proteins has not been fully characterized, although the Trp residue is frequently located near disulfide bonds. To improve our understanding of the mechanisms of degradation and stability of protein pharmaceuticals, we have exposed disulfide-containing, Trp-containing, and disulfide and Trp-containing peptides, and an IgG1 molecule to light at λ = 254 nm and/or λmax = 305 nm. By mass spectrometry, chemical derivation, and NMR analysis, we observed a novel Cys crosslinked product after photoirradiation, tentatively identified as isothiazole-3(2H)-one. By mass spectrometry, we observed cleavage of the Trp side chain to Gly and/or Gly hydroperoxide in IgG1 at three separate Trp residues located in both the heavy and light chains, all of which were within close proximity to a disulfide bond. We also detected the cleavage of the Trp side chain to Gly and/or Gly hydroperoxide in two model peptides. In a third model peptide, we observed the cleavage and trapping of the Trp side chain by nearby Lys and Tyr residues. The Cys crosslink and Trp cleavage products highlight the damage light exposure can have by not only inducing a significant amino acid modification, but also leading to protein aggregation or amino acid hydroperoxides that have the potential to induce additional protein oxidation.
en
Copyright held by the author.
Pharmaceutical sciences
Chemistry
Physical chemistry
Disulfide bonds
IgG1
Model peptides
Monoclonal Antibodies
Photochemistry
Tyrptophan
Novel Cys crosslinks and Trp side chain cleavages in proteins and peptides exposed to light
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/24831/1/Bane_ku_0099D_13862_DATA_1.pdf
File
MD5
5a9ff2946fcc780b4db6543c539d0685
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Bane_ku_0099D_13862_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/24831/2/Bane_ku_0099D_13862_DATA_1.pdf.txt
File
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91f7dca13ab1f1df10fad7b851e68011
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Bane_ku_0099D_13862_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/278302020-07-09T21:32:39Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
Pace, Samantha
cmtemember
Middaugh, C. Russell
cmtemember
Hageman, Michael
cmtemember
Siahaan, Teruna
cmtemember
Ritcher, Mark
2019-05-10T16:04:24Z
2019-05-10T16:04:24Z
2018-08-31
http://dissertations.umi.com/ku:16116
http://hdl.handle.net/1808/27830
Antibody-based therapeutics continue to be a fast growing field in pharmaceutics due to their increased selectivity for a specific target over small molecule drugs. Antibody solutions are often formulated at high protein concentrations in order to achieve low injection volumes, especially for subcutaneous administration, which can cause many challenging problems when it comes to stabilization. The instability of antibodies can often lead to aggregation which can occur during many parts of the manufacturing process including purification, fill-finish, shipping and storage. Aggregation of antibodies can cause many problems such as not injecting the proper dose, due to a decrease in the protein’s concentration, or causing immunogenic responses that may affect the safety or efficacy of the drug potentially causing harm to patients. Therefore, the aggregation pathway(s) of antibody drug candidates need to be characterized in great detail and well understood before they reach the market. Currently, several common analytical techniques are being used to distinguish the amount and size of aggregation impurities produced when an antibody undergoes accelerated stresses during formulation development. However, more novel techniques are needed to get a better, more in-depth understanding of the types of aggregates formed along of the aggregation pathway. The development of novel techniques to screen antibody stability and aggregation propensities can not only elucidate degradation mechanisms that proteins undergo throughout the lifetime of the drug, it can also allow us to better understand effective ways to increase the shelf-life and maintain product safety. In this study, various monoclonal antibodies (mAb) and bispecific antibodies (biAb) were examined under varying stress conditions and their physical stability monitored using conventional and novel techniques. New techniques examined include a high throughput GroEL-based BLI (Biolayer interferometry) assay that helps identify less stable antibodies, formulations (excipients, pH values), and storage conditions (temperatures) by being able to detect pre-aggregate species forming prior to more established techniques show the formation of larger sized aggregates (methods such as size exclusion chromatography and micro-flow digital imaging). Another novel technique examined in these studies is the use of hydrogen-deuterium exchange mass spectrometry, which is used to identify problematic portions of the antibody molecule, by monitoring changes in local flexibility or rigidity, when exposed to different excipients and pH levels. Finally, the use of Langmuir trough to examine interfacial and intermolecular interaction properties of various antibodies and formulation conditions was evaluated. Understanding antibody molecules tendencies to drive to the air-water interface or have intermolecular interactions can predict physical instability problems throughout the purification process and during long term storage conditions. This type of aggregation risk assessment during early formulation development can decrease the resources spent on protein drug candidates that will be problematic. Each of these novel analytical techniques can increase the understanding of antibody instability issues in solution, and therefore, allow for an increased likelihood of successful drug design and development overall.
en
Copyright held by the author.
Pharmaceutical sciences
Aggregation
EVALUATING NOVEL ANALYTICAL TECHNIQUES TO ASSESS THE INITIAL STEPS OF PROTEIN AGGREGATION USING VARIOUS ANTIBODY SOLUTIONS
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/27830/1/Pace_ku_0099D_16116_DATA_1.pdf
File
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Pace_ku_0099D_16116_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/27830/2/Pace_ku_0099D_16116_DATA_1.pdf.txt
File
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oai:kuscholarworks.ku.edu:1808/261562018-04-19T20:16:39Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Lunte, Susan M
author
Mann, Benjamin
cmtemember
Stobaugh, John F
cmtemember
Aldrich, Jane V
2018-03-09T22:38:32Z
2018-03-09T22:38:32Z
2016-12-31
http://dissertations.umi.com/ku:15033
http://hdl.handle.net/1808/26156
Pharmaceutical agents targeting the μ opioid receptors (MOR) have been widely used in the treatment and management of pain. However, serious side effects and the prevalence of abuse have complicated their administration. This has increased the interest of developing pharmaceutical agents that selectively bind to the κ opioid receptors (KOR). Recent investigation has determined that KOR agonists exhibit a decreased liability for addiction as well as respiratory depression in comparison to MOR agonists. Selectively binding antagonists to the KOR have only been utilized historically as pharmacological tools. Additionally, KOR antagonists show promising potential in therapeutic treatment of depression and anxiety, as well as opiate and cocaine addiction. KOR antagonists that are metabolically stable have been shown to penetrate the CNS. However, peptide-based KOR-selective antagonists are metabolized by proteases and are expected to have a shorter activity than non-peptide KOR-selective antagonists with increased metabolic stability. Through the incorporation of unnatural amino acids as well as conformational constraints in the C terminus, zyklophin experiences increased enzymatic stability. Initial testing has shown that zyklophin crosses the blood brain barrier to antagonize the KOR in the CNS with in vivo administration and that its duration of activity after a system dose is less than 12 hours, whereas a non-peptide KOR antagonist, such as nor-BNI, exhibits duration of activity weeks after a single dose is administered. This prolonged activity complicates its use as a pharmacological tool and as a potential therapeutic agent whereby increasing the importance of peptide-based KOR antagonist. Currently, the FDA has not approved a drug for the prevention of relapse due to cocaine addiction. Peptide-based drugs have been shown to be successful pharmaceutical agents exhibiting high activity, high specificity, low toxicity, and minimal drug-drug interaction. Due to modifications of the C-terminus, zyklophin has an increased metabolic stability. Thus, zyklophin is a good lead compound for the treatment of cocaine addiction and relapse.
en
Copyright held by the author.
Pharmaceutical sciences
Addiction
Cocaine
Dynorphin
Kappa Opioid Receptor
LC-MS/MS
Pharmacokinetics
Determination of Pharmacokinetic Parameters of Subcutaneous Zyklophin by Quantitative Determination of Zyklophin in Mouse Plasma by LCMS/MS Analysis For Assessment As A Potential Therapeutic Agent In The Treatment of Cocaine Addiction
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/26156/1/Mann_ku_0099M_15033_DATA_1.pdf
File
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Mann_ku_0099M_15033_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/26156/2/Mann_ku_0099M_15033_DATA_1.pdf.txt
File
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6b4576d96838ee1ec761503c099172fe
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Mann_ku_0099M_15033_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253832018-09-20T19:46:20Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Tolbert, Thomas
author
Al-Kinani, Khalid Kadhem Abed
cmtemember
Middaugh, C.Russel
cmtemember
Siahaan, Teruna
cmtemember
Wang, Michael
cmtemember
Saint Onge, Jarron
2017-11-16T03:56:59Z
2017-11-16T03:56:59Z
2017-08-31
http://dissertations.umi.com/ku:15473
http://hdl.handle.net/1808/25383
Immunoglobulin G (IgG) is a complex glycoprotein that is largely being used in the development of antibody-based therapeutics to treat a variety of diseases such as cancers, autoimmune diseases, and infectious diseases. A major challenge in developing such therapeutics originates from the heterogeneity of the Asn297 glycan of IgG. This sugar part (Asn297 glycan) of IgG has been shown to play an important role in the antibody properties such as antibody stability, effector functions, solubility, pharmacokinetics, and immunogenicity. To study the effect of Asn297 glycan composition on the properties of the human IgG2 (a preferred IgG subclass for developing antibody-based therapeutics when the antibody effector functions are not required), we developed an approach to produces homogeneous IgG2 Fc glycoforms. Studying these homogeneous IgG2 Fc glycoforms suggested that enriching the core fucose within IgG2 Asn297 glycan could add more advantages to developing IgG2-based therapeutics by providing more reduction in any possible undesirable effector functions of these therapeutics. The in vitro enzymatic synthesis developed here also enabled studies of different glycosylation sites accessibility to glycosyltransferase and expanded our understanding of the glycosylation heterogeneity. The Asn297 glycan also offers a great opportunity in developing antibody drug conjugates (ADCs), a therapeutic modality where a toxic payload is conjugated to IgG. The early ADC development relied on conjugating the payload non-specifically through either the lysine or cysteine residues of IgG using conventional chemistries. Producing ADCs in this way, results in heterogeneous products. ADC heterogeneity usually translates into poor pharmacokinetics, stability, and efficacy. In this work, we developed a chemoenzymatic synthesis platform to functionalize the Asn297 glycan in a novel way and use it as a specific site for conjugation. The work involved using and optimizing click chemistry reactions for conjugating different linkers on IgG2 Fc. This approach enabled us to produce conjugates with excellent homogeneity. Subsequent studies of these conjugates showed the utility of the approach followed here in making of site-specific conjugates with good properties and the possibility of following this approach in designing and testing site-specific ADCs during the process of developing next generation ADCs.
en
Copyright held by the author.
Pharmaceutical sciences
Antibody
Chemoenzymatic synthesis
Fucosylation
FUT8
Glycosylation
Site-Specific ADC
Modifying the Fc Asn297 Glycan of Human IgG2 Subclass for Improved Antibody Therapeutics and Design of Site-Specific Antibody Drug Conjugates
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25383/1/AlKinani_ku_0099D_15473_DATA_1.pdf
File
MD5
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AlKinani_ku_0099D_15473_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25383/2/AlKinani_ku_0099D_15473_DATA_1.pdf.txt
File
MD5
de0449e95558e19120059343905743b7
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AlKinani_ku_0099D_15473_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216562018-01-31T20:07:47Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory J
author
Thati, Sharadvi
cmtemember
Forrest, Laird
cmtemember
Siahaan, Teruna
cmtemember
Tolbert, Thomas
cmtemember
Detamore, Michael
2016-10-11T19:04:36Z
2016-10-11T19:04:36Z
2016-05-31
http://dissertations.umi.com/ku:14563
http://hdl.handle.net/1808/21656
Soluble antigen arrays (SAgAs) were used to treat experimental autoimmune encephalomyelitis (EAE), which is a mouse model for multiple sclerosis (MS). SAgAs offer a targeted therapy for MS, which is not present in current therapies. The different routes of administration, injection volume, dosing amount, and dosing schedule were explored to find that pulmonary instillation of SAgAs at 50 μL on a 200 nMol PLP basis on days 4, 7, and 10 of the study are most efficacious. With the next study, the different components of SAgAs (hyaluronic acid, PLP, LABL, and bifunctional peptide inhibitor) were also investigated via pulmonary delivery to find that PLP and SAgAs decreased the symptoms of EAE the most. PLP, HA-PLP, and SAgAs were further explored either via subcutaneous injection or pulmonary instillation to find that HA-PLP and SAgAs decreased disease progression in mice with EAE. Cytokine panels were also used to determine if tolerance was induced in these mice via the measurements of pro- and anti-inflammatory cytokines. Lastly, lung histology was explored to find signs of inflammation. Overall, SAgAs are found to be very efficacious in treating mice via PI and the presence of PLP makes a big difference. Other methods like the presence of regulatory T cells need to be used to find additional signs of tolerance induction in future studies.
en
Copyright held by the author.
Pharmaceutical sciences
experimental autoimmune encephalomyelitis
hyaluronic acid
multiple sclerosis
tolerance induction
Optimizing the Treatment of Experimental Autoimmune Encephalomyelitis via Pulmonary Delivery of Soluble Antigen Arrays
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21656/1/Thati_ku_0099D_14563_DATA_1.pdf
File
MD5
4eba8c8b325d9dd3326b80c1c1200736
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Thati_ku_0099D_14563_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21656/2/Thati_ku_0099D_14563_DATA_1.pdf.txt
File
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Thati_ku_0099D_14563_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216232020-10-21T15:25:56Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Siahaan, Teruna J
author
AlSalman, Mohammed Sulieman
cmtemember
Tolbert, Thomas
cmtemember
Krise, Jiff
2016-10-11T15:05:50Z
2016-10-11T15:05:50Z
2013-12-31
http://dissertations.umi.com/ku:13046
http://hdl.handle.net/1808/21623
The blood brain barrier (BBB) is a key role in delivering medication to the brain; if the drug molecules can overcome this obstacle, many brain diseases (i.e., Alzheimer's, Parkinson's, and brain tumor) can be effectively treated. E-cadherin is important in forming cell-cell adhesion in intercellular junctions of the biological barriers (i.e., intestinal mucosa and BBB). Cadherin peptides (HAV6 and ADTC5) have been shown to modulate the BBB in the cell culture and in in-situ rat brain perfusion models. The hypothesis is that cadherin peptides modulate the tight junctions of the BBB by binding to the EC1 domain of E-cadherin. Thus, the objective of this project is to determine the dissociation constants (Kds) of linear and cyclic cadherin peptides (i.e., HAV- and ADT-peptides) to the expressed EC1 domain of E-cadherin using circular dichroism (CD) spectroscopy. The data show that the cyclic HAVc3 peptide (Kd = 66.7±18.0 nM) has better binding property to the EC1 domain than the linear HAV6 peptide (Kd = 120.1±11.9 nM). Cyclic ADTC5 (Kd = 50.2± 11 nM) has lower dissociation constant than ADTC1 (Kd = 119.7± 16 nM). Mutation of the valine residue in ADTC5 to glutamic acid (ADTC7; Kd = 0.43± 0.050 nM) and threonine (ADTC8; Kd = 0.45±0.012) makes the peptides to have 100-fold tighter binding compared to the EC1 domain. Mutation of the valine residue in ADTC5 to a tyrosine residue (ADTC9; Kd = 0.038± 0.009) increases binding to the EC1 domain by 1000-fold. Finally, mutation of the valine residue to arginine demolishes the activity of ADTC10. In the future, the activity of ADTC9 to modulate the BBB will be compared to ADTC5 in in vitro and in vivo models of the BBB.
en
Copyright held by the author.
Pharmaceutical sciences
Biochemistry
Binding studies of E-Cadherin peptides to the EC1 domain of E-Cadherin
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21623/1/AlSalman_ku_0099M_13046_DATA_1.pdf
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URL
https://kuscholarworks.ku.edu/bitstream/1808/21623/2/AlSalman_ku_0099M_13046_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/261622018-04-19T20:25:51Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Krise, Jeffrey
advisor
Kelley, Robert
author
Wang, Yue
cmtemember
Stobaugh, John
2018-03-09T22:54:44Z
2018-03-09T22:54:44Z
2017-12-31
http://dissertations.umi.com/ku:15609
http://hdl.handle.net/1808/26162
A better understanding of the molecular attributes contributing to vitreal elimination half-life could enable the design of improved therapeutics for the treatment of human posterior segment ocular disease. Here we have used pharmacokinetics (PK) studies in rabbits to probe the contribution of electrostatic charge, hydrophobicity, and hydrodynamic size to vitreal clearance of antibody fragments (Fabs). Comparing Fabs of diverse binding targets, we find that vitreal half-life is not strongly correlated with measured isoelectric point (pI) or the hydrophobicity index (HI) of the variable domain unit (Fv) calculated from the amino acid sequence. We completed two systematic studies of molecule charge and hydrophobicity by determining the vitreal half-life of variants of ranibizumab. Charge or hydrophobicity was altered through introduction of amino acid changes in two of the hypervariable regions of the light chain. Equivalent vitreal pharmacokinetics were observed for ranibizumab and these variants with pIs in the range 6.8 – 10.2 and Fv HI varied in the range 1090-1296. Finally, a previously observed linear dependence between vitreal half-life and hydrodynamic radius, determined using light scattering measurements, has been extended to a broader range. These results indicate that diffusive properties of antibody Fabs, as quantified by the hydrodynamic radius, make a key contribution to vitreal elimination whereas minor or negligible contributions arise from differences in charge or hydrophobicity in the ranges tested in these studies.
en
Copyright held by the author.
Pharmaceutical sciences
Antibody Fab Charge
Hydrodynamic Size
Hydrophobicity
Vitreal Elimination
Vitreal Half-life
Vitreous Pharmacokinetics
Influence of antibody Fab charge, hydrophobicity, and hydrodynamic size on vitreous pharmacokinetics in rabbits
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/26162/1/Wang_ku_0099M_15609_DATA_1.pdf
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URL
https://kuscholarworks.ku.edu/bitstream/1808/26162/2/Wang_ku_0099M_15609_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/302002021-03-05T16:54:48Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Hageman, Michael J
advisor
Ohtake, Satoshi
author
Langford, Alex
cmtemember
Krise, Jeffrey P
2020-03-28T20:51:54Z
2020-03-28T20:51:54Z
2019-12-31
http://dissertations.umi.com/ku:16810
http://hdl.handle.net/1808/30200
https://orcid.org/0000-0001-9456-2925
The biopharmaceutical industry has reached new frontiers in its ability to produce complex novel modalities for therapeutic application. Novel cell-based therapies offer a promising treatment for cancer by enabling T cells to target tumor antigens through ex vivo engineering of cell receptors and intracellular signaling domains. Development of cell-based therapeutics for clinical and commercial application requires successful manufacturing, stability, and transport. Since significant cell degradation occurs without the use of cryopreservation techniques, cells must be stored at extremely low temperatures (<-130 °C). Successful preservation of human T cells in the dried state provides the opportunity for non-vapor phase storage of the final product. Herein, several key factors are discussed and evaluated for T cell stabilization in the dried state, including the presence of intracellular stabilizer, cell health prior to drying, reconstitution procedure, and formulation components. Residual water content of dried preparations was balanced between increased glass transition temperatures at low moisture and reduced process loss at high moisture. A vacuum-foam drying method demonstrated improved process recovery and increased stability at refrigerated storage compared to other drying techniques. These findings demonstrate the feasibility of drying human T cells with retained membrane integrity after drying and rehydration.
en
Copyright held by the author.
Pharmaceutical sciences
Drying technologies
Human T cells
Membrane integrity
Reconstitution
Trehalose
Vacuum-foam drying
Preservation of Human T Cell Membrane Integrity after Drying and Rehydration
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/30200/1/Langford_ku_0099M_16810_DATA_1.pdf
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URL
https://kuscholarworks.ku.edu/bitstream/1808/30200/2/Langford_ku_0099M_16810_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/278042019-08-27T18:09:08Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
TOPRANI, VISHAL M
cmtemember
Middaugh, C.Russell
cmtemember
Hageman, Michael J
cmtemember
Siahaan, Teruna J
cmtemember
Dhar, Prajnaparamita
2019-05-07T16:23:16Z
2019-05-07T16:23:16Z
2018-05-31
http://dissertations.umi.com/ku:15771
http://hdl.handle.net/1808/27804
Protein based vaccine antigens and adjuvants offer several advantages over inactivated or live attenuated viruses and bacteria including ease to manufacture and improved safety. Due to the structural complexity and inherent marginal stability of protein based antigens and adjuvants, however, extensive analytical characterization and robust formulation development approaches are required to develop a stable, potent and safe vaccine dosage form for use in patients. In addition, the elucidation of physical and chemical instability pathways of protein antigens plays a key role in their formulation design, and are generally studied using numerous biophysical and analytical techniques, during forced degradation as well as accelerated and real-time stability studies. Furthermore, analytical comparability assessments form a cornerstone for assessing vaccine quality (including stability) between pre-change versus post-change drug products during development and scale-up of manufacturing processes. This Ph.D. thesis research work is aimed to better understand vaccine stability from three different pharmaceutical development aspects including analytical characterization, formulation development and comparability assessments. In addition, this work contributes towards the ongoing efforts to discern interrelationships of a protein antigen’s physicochemical properties to critical quality attributes of various vaccine candidates. As a part of this work, we developed and utilized improved analytical tools for formulation development and comparability assessments. For example, a scaled down micro-polyethylene glycol (PEG) induced precipitation assay was developed to determine apparent solubility of proteins using less than a milligram of material (as described in Chapter 2). This assay will be helpful in apparent solubility measurements during pharmaceutical development of proteins, especially, in early stages where limited material is available. In addition, analytical characterization of three different protein virus-like particle antigens (equine encephalitis virus-like particles, EEV) and a protein adjuvant (double mutant heat labile toxin, dmLT) by various biophysical and biochemical techniques was performed. The analytical characterization of the physical stability profile of the VLPs and physicochemical stability profile of dmLT, along with the role of pharmaceutical excipients in stabilizing their respective formulations, was evaluated. Lastly, an analytical comparability assessment involving five CRM197 carrier protein molecules was performed to better understand the effect of different manufacturing processes on the physicochemical and in vitro antigenic properties of the carrier protein. Currently, the protein adjuvant dmLT is an oral vaccine candidate for enterotoxigenic E.coli (ETEC) and is under clinical development. For this project, the primary and higher-order structures, physicochemical and conformational stability profiles of dmLT were assessed as described in Chapter 3. The physicochemical degradation pathways of dmLT included protein aggregation, glycation and oxidation. By identifying the physicochemical degradation pathways of dmLT using newly developed stability-indicating analytical methods, a more stable candidate bulk formulation of dmLT was developed that protected dmLT against conformational destabilization, freeze-thaw stress, aggregation/particle formation and chemical degradation. As described in Chapter 4, this work contributed to ongoing efforts to develop a vaccine against three strains of equine encephalitis (Eastern, Western and Venezuelan). Here, analytical characterization of three different monovalent VLPs was performed to identify structural alterations induced by thermal and pH stress. A candidate formulation mitigating thermal and aggregation instabilities of the VLPs was also developed. The candidate formulation showed a good maintenance of stability at all storage temperatures (40 to -80oC), with the exception of a distinct instability at -20°C; the mechanism of which is discussed in detail in Chapter 4. The interaction of both monovalent and trivalent VLP formulation with aluminum salt adjuvants was also studied to better understand the binding interactions of the VLPs with the adjuvant and its implications on future drug product development are discussed. Lastly, a comprehensive and detailed analytical characterization of CRM197 molecules from different manufacturers and expression hosts was executed as described in Chapter 5. This work provides an initial basis to eventually develop global manufacturing specifications to ensure the quality of the bulk CRM197 proteins from a variety of manufacturers. Furthermore, the high similarities between five different recombinant CRM197 expressed in the native host (C.diptheriae) vs. alternative hosts (E.coli or P.fluorescens), as demonstrated in this work, is a first step that will help facilitate lower cost CRM197 bulk production, with the long term goal to develop lower-cost polysaccharide conjugate vaccines for the developing world.
en
Copyright held by the author.
Pharmaceutical sciences
Adjuvant
Biophysical
Comparability
Formulation
Stability
Vaccines
TOWARDS A BETTER UNDERSTANDING OF VACCINE STABILITY AS APPLIED TO PHARMACEUTICAL DEVELOPMENT OF VARIOUS RECOMBINANT PROTEIN VACCINE CANDIDATES
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/27804/1/TOPRANI_ku_0099D_15771_DATA_1.pdf
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https://kuscholarworks.ku.edu/bitstream/1808/27804/2/TOPRANI_ku_0099D_15771_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/295482020-10-13T15:28:11Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Schoeneich, Christian
advisor
Stefanidis, Dimitrios
author
Forseth Millard, Kristen
cmtemember
Stobaugh, John
cmtemember
Schoeneich, Christian
cmtemember
Stefanidis, Dimitrios
2019-09-06T19:33:23Z
2019-09-06T19:33:23Z
2019-05-31
http://dissertations.umi.com/ku:16418
http://hdl.handle.net/1808/29548
https://orcid.org/0000-0002-8408-2618
The reactivity of 4-morpholinoaniline with water was examined in aqueous solutions at pH 1 – 4. Two dissociation constant values were identified for 4-morpholinoaniline using spectrophotometric titration: pKa1, which was assigned to the aniline ammonia nitrogen, was 1.8 and pKa2, assigned to the morpholine nitrogen, was 4.9. At pH < pKa1, 4-morpholinoaniline reacted with water to form 4-morpholinophenol, which further degraded to hydroquinone. The hydrolytic degradation reactions of 4-morpholinoaniline to 4-morpholinophenol and 4-morpholinophenol to hydroquinone both exhibited pseudo-first order kinetics under these reaction conditions. 4-Morpholinophenol is proposed to form by nucleophilic aromatic substitution of the aniline ammonia by water via an intermediate whose electron-rich aromatic ring is electrostatically stabilized by the positive charge on the morpholino nitrogen and the positive charge on the incoming nucleophilic water molecule. As pH exceeded pKa1 and the aniline ammonia nitrogen was deprotonated, the nucleophilic aromatic substitution reaction was disfavored and accounted for less than 10% of 4-morpholinoaniline degradation at pH ≥ 2.5. Instead, 4-Morpholinoaniline degradation in these higher pH aqueous solutions yielded multiple degradation products, and the kinetics of 4-morpholinoaniline degradation were more complicated than zero-, first-, or second-order. Characterization and structural identification of the major degradation product observed in these higher pH solutions yielded a highly conjugated molecule that appears to be a dimerization product. Without identification of intermediates or additional degradation products observed by chromatography, the mechanism by which this product forms could not be resolved; however, metal catalysis and direct reaction of 4-morpholinoaniline with 4-morpholinophenol were disproven.
en
Copyright held by the author.
Pharmaceutical sciences
4-morpholinoaniline
aqueous degradation
degradation kinetics
nucleophilic aromatic substitution
Small molecule kinase inhibitors
The Degradation of 4-Morpholinoaniline in Aqueous Solution
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/29548/1/ForsethMillard_ku_0099M_16418_DATA_1.pdf
File
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URL
https://kuscholarworks.ku.edu/bitstream/1808/29548/2/ForsethMillard_ku_0099M_16418_DATA_1.pdf.txt
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oai:kuscholarworks.ku.edu:1808/216392020-10-22T14:14:53Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory
author
Pornputtapitak, Warangkana
cmtemember
Stella, Valentino J.
cmtemember
Forrest, Laird
cmtemember
Wang, Zhuo
cmtemember
Southard, Marylee
2016-10-11T16:16:02Z
2016-10-11T16:16:02Z
2014-05-31
http://dissertations.umi.com/ku:13328
http://hdl.handle.net/1808/21639
The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as `NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a Monodose® inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the Monodose® inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state while milled ITZ NanoClusters maintained the crystalline character. Overall, NanoClusters prepared by various processes represent a potential engineered drug particle approach for inhalation therapy since they provide effective aerosol properties and stability due to the crystalline state of the drug powders. Future work will continue to explore formulation and delivery performance in vitro and in vivo.
en
Copyright held by the author.
Pharmaceutical sciences
dry powder
inhalation
mechanical ventilation
NanoCluster
NanoClusters Enhance Drug Delivery in Mechanical Ventilation
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21639/1/Pornputtapitak_ku_0099D_13328_DATA_1.pdf
File
MD5
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URL
https://kuscholarworks.ku.edu/bitstream/1808/21639/2/Pornputtapitak_ku_0099D_13328_DATA_1.pdf.txt
File
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oai:kuscholarworks.ku.edu:1808/106242020-09-22T13:30:31Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Hu, Lei
cmtemember
Volkin, David B.
cmtemember
Laurence, Jennifer S.
cmtemember
Lunte, Susan M.
cmtemember
Johnson, Carey
2013-01-20T15:04:39Z
2013-01-20T15:04:39Z
2012-12-31
http://dissertations.umi.com/ku:12480
http://hdl.handle.net/1808/10624
The conformational stability of a protein is a fundamental concern in formulating protein drug products, and development of analytical methods for stability characterization is critical for this purpose. Because of the complexity, relatively lower stability and variety of degradation pathways of protein molecules, the selection of appropriate analytical methods is important and needs to meet specific requirements for stability testing, screening formulations, as well as for product release. To characterize the stability of proteins comprehensively, the conformational stability of proteins is typically investigated using a variety of biophysical measurements as a function of environmental stresses such as pH and temperature. These multiple techniques typically require a variety of single function instruments. Each technique, however, provides information on only a particular aspect of a protein's higher order structural integrity (secondary, tertiary, and quaternary). The combination of different techniques provides a better understanding of the overall conformational stability of a protein, although these measurements typically require large sample quantities and long experimental times. Therefore, the development of high throughput methods to comprehensively characterize protein stability with a single multifunctional instrument is needed to save both materials and time. In the first part of my work (Chapters 2-4), a new methodology is developed to obtain protein conformational stability data simultaneously, including UV absorption, light scattering, and near- and far- UV CD by employing a multimodal spectrometer (Chapter 2). Fluorescence spectral data are also collected on the same instrument although not simultaneously. The method is developed by examining the thermal and pH stability of four model proteins. Results show reproducible and accurate data using this single instrument, and data collection is rapid with minimal protein sample requirements. This study also illustrates the application of this method for generating empirical phase diagrams (EPDs) to better characterize the overall conformational stability of proteins. This new approach facilitates the rapid characterization of protein structure and stability data in a single instrument. It is useful for analysis of unknown proteins, as well as screening of solution conditions to optimize stability for protein therapeutic drug candidates. I also describe the application of this new method (Chapter 2) to characterize the stability of the recombinant anthrax protective antigen (rPA) and its 2-fluorohistidine (2-FHis) labeled analogue (Chapter 3). Protective antigen (PA) is a key, non-toxic component of the anthrax toxin. It is also a primary antigenic component of the current formaldehyde inactived anthrax vaccine. An analogue of PA has been recently shown to block key steps in pore formation in the process of inducing cytotoxicity in cells. Thus, it can potentially be used as an antitoxin or a vaccine. This analogue is synthesized by incorporating the unnatural amino acid 2-fluorohistidine (2-FHis). In this study, the effects of 2-FHis labeling on rPA antigen stability and its dynamic properties are investigated by various experimental techniques. Physical stability profiles of the two proteins (rPA and 2-FHis rPA) are created by using the empirical phase diagram (EPD) approach, and stability differences between them are identified. Results show that rPA and 2-FHis rPA have similar stability at pH 7-8. With decreasing pH, however, 2-FHis rPA is found to be more stable. Intramolecular dynamics sensitive measurements of the proteins at pH 5 find that 2-FHis rPA has increased internal mobility under acidic pH conditions. The stability and dynamics characterization data provide information useful for the formulation development of 2-FHis rPA as a more stable antigen for vaccine development. In addition, the new multimodal spectrometer method (Chapter 2) is coupled to other techniques such as SDS-PAGE, static light scattering, dynamic light scattering, isoelectric focusing, size-exclusion liquid chromatography as well as micro flow imaging to characterize the stability of dominant-negative inhibitor (DNI) protein (Chapter 4). DNI is a translocation-deficient mutant of PA with double mutations of K397D and D425K. It is a promising candidate for treatment or prevention of anthrax disease, which can potentially provide high immunogenicity in vaccines and therapeutic activity in antitoxic therapy. The lyophilized protein formulated with common excipients was stored for about 8 years at refrigerated temperature. In my study, samples were placed at two selected temperatures (40 and 70 oC) for one to four weeks, and analyzed by the above mentioned methods. The chemical stability (deamidation) was also evaluated using capillary isoelectric focusing (cIEF). Results show that the thermally stressed DNI protein retained its native conformation at temperatures as high as 70 oC for one month. The long-term stability of DNI was also demonstrated for samples stored at 4 oC for about 8 years. These data provide valuable and encouraging information for development of an alternative recombinant anthrax vaccine using a mutated anthrax protective antigen. In the second part of my work (Chapters 5, 6), the research focuses on stability characterization and formulation of a pneumolysin mutant (L460D), a candidate for a pneumococcal vaccine (Chapter 5), and two virus-like particles (VLPs) as candidates for use against human filovirus infection (Ebola and Marburg, Chapter 6). In these studies, a three step experimental design is employed in the characterization and formulation processes. First, the conformational stability of the pneumolysin mutant and VLPs are characterized under stressed environmental conditions (pH 3-8 and temperature 10-87.5 oC) by different analytical methods. Second, different types of biophysical data are summarized by using the empirical phase diagram (EPD) method, which is also used to define conditions for an excipients screening study. Finally, the pharmaceutical excipients are screened and potential stabilizers are identified by appropriate assays. In these studies, critical parameters (such as solution pH, temperature, ionic strength and stabilizers) affecting the stability of proteins are defined. These studies provide a basis for selection of optimized solution conditions for further long-term stability studies of pneumococcal antigens and Ebola and Marburg virus-like particles, and illustrate the utility of the multimodal spectrometer and EPD analysis for vaccine formulation development.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Development and Application of a High Throughput Methodology to Characterize and Formulate Protein-Based Therapeutics
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10624/1/Hu_ku_0099D_12480_DATA_1.pdf
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oai:kuscholarworks.ku.edu:1808/253862018-09-20T19:46:55Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Volkin, David B
author
More, Apurva Shirish
cmtemember
Middaugh, Russell C
cmtemember
Tolbert, Thomas J
cmtemember
Weis, David D
cmtemember
Deeds, Eric J
2017-11-16T04:06:50Z
2017-11-16T04:06:50Z
2017-08-31
http://dissertations.umi.com/ku:15492
http://hdl.handle.net/1808/25386
https://orcid.org/0000-0001-5159-7861
Therapeutic efficacies of IgG monoclonal antibodies (mAbs) depend on their physicochemical structural integrity, stability, flexibility and biological functionality. IgG-Fc glycosylation at Asn-297 is important for the structural integrity and effector function activities of IgG mAb therapeutics and is a key contributor of their heterogeneity. Molecular heterogeneities (like glycosylation) must be closely monitored and assessed during development of mAbs from drug candidate to marketed product and during biosimilar development. A variety of techniques are being developed to monitor chemical structure and glycosylation profiles of mAbs, however, novel analytical techniques are needed to better understand the effects of glycosylation on their complex higher order structures and dynamics for their effective development. In comparability and biosimilarity exercises, analytical characterization tools serve as the foundation for establishing similarity between pre change versus post change products and biosimilar versus innovator product. Hence, better tools are needed for drawing comparisons between the results. In this study, four highly purified, well-defined recombinant IgG1-Fc glycoform variants (High-mannose-Fc (HM-Fc), Man5-Fc (truncated glycoform), GlcNAc-Fc (truncated glycoform), and non-glycosylated-Fc (N297Q-Fc) were produced which served as model glycoproteins to study the effect of IgG1-Fc N-linked glycosylation on various pharmaceutical properties. This work explores the utility of yeast expression along with in vitro enzymatic digestion for obtaining homogenous glycoform profiles of IgG Fc glycans; which is extremely challenging to achieve considering the observed inherent glycan heterogeneity in expression hosts. We developed and utilized various orthogonal analytical techniques to explore the relationship between glycosylation and physical stability of these IgG1-Fc glycoforms and compared their physical stability in two different formulations to mimic follow on therapeutics or biosimilars that might be formulated differently. Hence, this study contributed towards the ongoing development of data visualization and mathematical modeling tools for comparability and biosimilarity assessments. To simulate a more practical biosimilar comparability scenario, various mixtures of the four glycoforms were made to mimic heterogeneity found in biosimilars. The physical stability of these mixtures was evaluated by combination of high-throughput biophysical techniques. The ability of various biophysical techniques to demonstrate the estimated differences between the physical stability of the mixtures was examined. Even though the biophysical techniques utilized in this study are the most commonly used tools in the industry, these are low in resolution and only show the average conformational outcome. Hence, to obtain high-resolution peptide-level information on changes in local dynamics because of changes in IgG1-Fc glycans, hydrogen exchange (HX-MS) in combination with pepsin proteolytic digestion and liquid chromatography-mass spectrometry (LC-MS) was utilized. Previous HX-MS studies on IgG mAbs in our laboratory showed an increased flexibility of a particular peptide segment in the Fc region in the presence of excipients and salts. This result was attributed to the disruption in packing of the heterogeneous glycan structures with the Fc region. Another goal of this dissertation was to explore the mechanisms of interactions between glycans and IgG1-Fc. The correlations between glycosylation and physicochemical structure, stability and flexibility of well-defined IgG1-Fc glycoforms in this dissertation, will serve as important tools to enable rational design and optimization of stable IgG formulation conditions to avoid conformational destabilization and aggregation issues during their manufacture, long-term storage and administration. The extensive analytical characterization approach utilized in this dissertation will contribute towards the ongoing development of statistical tools as required by the US Food and Drug Administration (FDA), for similarity analysis between biosimilar and innovator therapeutics.
en
Copyright held by the author.
Pharmaceutical sciences
Chemistry
Antibody
Biosimilarity
Flexibility
Glycosylation
Physical Stability
Protein Characterization
ELUCIDATION OF THE IMPACT OF N-GLYCAN STRUCTURE ON PHYSICAL STABILITY AND LOCAL FLEXIBILITY OF WELL-DEFINED IgG1-Fc GLYCOFORMS FROM A PHARMACEUTICAL DEVELOPMENT PERSPECTIVE
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25386/1/More_ku_0099D_15492_DATA_1.pdf
File
MD5
0bf6f4bd8306d7b6ca60bba128674bcd
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More_ku_0099D_15492_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25386/2/More_ku_0099D_15492_DATA_1.pdf.txt
File
MD5
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text/plain
More_ku_0099D_15492_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253852018-12-14T16:46:43Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Siahaan, Teruna
advisor
Chadwick, Jennifer
author
McNiff, Michaela L.
cmtemember
Siahaan, Teruna
cmtemember
Chadwick, Jennifer
cmtemember
Lamb, Audrey
cmtemember
Tolbert, Thomas
cmtemember
Picking, Wendy
2017-11-16T04:04:52Z
2017-11-16T04:04:52Z
2017-08-31
http://dissertations.umi.com/ku:15401
http://hdl.handle.net/1808/25385
Peptide and protein therapeutics encounter proteases at every stage of delivery, beginning at the site of administration and ending in the intracellular lysosomal compartment. An intact, stable molecule is desired upon administration, yet release of the payload or activation of the prodrug is necessary at the target site. Successful payload release or prodrug activation can be accomplished using enzymatic recognition sequences specific to proteases expressed in the tumor environment or within endocytic vesicles of the target cell. Control of the proteolytic susceptibility of biologics is essential to deliver a safe and effective molecule. Although degradation and release of proteins is desired at the target site, stability in the systemic circulation is required for successful delivery. Proteins and peptides often succumb to proteolysis in the systemic circulation, causing short half-lives due to their small size resulting in rapid filtration by the kidney. Proteases in the systemic circulation reduce half-life further through fragmentation rendering the biologic inactive. Achieving stability in the systemic circulation would greatly improve the half-life and efficacy of delivered biologics. Considering the half-life of peptides and proteins is especially important when they are used as diagnostic imaging agents. Contrast agents need a sufficient amount of time to accumulate at the target site to generate a high-quality image. Current contrast agents or diagnostic tracers consist of large chelators bound to lanthanide metals and are chemically conjugated to proteins creating a heterogeneous, unstable and toxic molecule. A common lanthanide ion used for imaging applications is gadolinium, which is often released from the chelator upon dilution into the body and accumulates in the kidney, causing renal toxicity. An improvement to chemically conjugated diagnostic imaging agents is to use a metal-binding tripeptide known as the claMP Tag. The claMP Tag consists of the amino acid sequence Asn-Cys-Cys and binds transition metals tightly at basic pH. Biocompatible transition metals such as copper and cobalt can be used to create a safe and effective molecular imaging agent. The claMP Tag enables design of a site-specific, homogenous and safe molecule, none of which is possible using current lanthanide binding tags. The compatibility of the claMP Tag within a metalloproteinase was investigated. Herein is the first application where the claMP Tag was placed within a molecule with a structural or catalytic metal-binding site. One hypothesis was that the claMP Tag would be able to interact with the catalytic Zn active site inhibiting the protease, while release of the claMP Tag could activate the enzyme. The claMP Tag followed by an eight-amino acid linker was engineered to the N-terminus of matrix metalloproteinase-8 (MMP-8). MMP-8 is very difficult to produce because of its inherent function of degrading extra cellular matrix (ECM) proteins and concomitant autoproteolysis. Production of this enzyme proved difficult as several fusion constructs were created and determined to be unsuccessful. A fusion construct consisting of a thioredoxin and S Tag, as well as, a polyhistidine tag enabled expression and purification of active, soluble MMP-8 in high yield. Studies were completed both with and without the claMP Tag placed inline with MMP-8. The claMP Tag had no structural or functional implications on the production of MMP-8. Further investigation of the claMP Tag as a modulator of enzymatic activity is of interest. Another focus of this work was to investigate the proteolytic stability of claMP-Tagged proteins. To investigate the proteolytic susceptibility of a protein containing the claMP Tag, a proof of concept study was designed to investigate the ability of the claMP Tag to inhibit adjacent proteolysis by a serum protease. The stability of the metal-bound and apo claMP Tag were compared to determine the effect of metal-binding on proteolysis. The claMP Tag inhibits proteolysis 3-fold compared to the control and use of the claMP Tag in applications creates a more proteolytically stable molecule. Following the proof of concept study, a targeted imaging agent was designed using the claMP Tag and the proteolytic stability of this molecule was analyzed. Previously, the claMP Tag was placed inline with the targeting protein, epidermal growth factor (EGF), and the structure and function of the protein were determined to be unaltered. EGF is a small protein that binds to the receptor EGFR and can be used to target EGFR (+) tumor cells, making EGF ideal for diagnostic imaging. One limitation is EGF has a very short half-life of only 3-7 min. Thus, to improve the half-life, addition of a polymer of amino acids, known as XTEN, was engineered to the C-terminus of EGF. Three EGF-claMP- XTEN molecules were created and analyzed for the structural and functional implications of the addition of XTEN and use of a relevant imaging agent, in this case cobalt, within the claMP Tag.
en
Copyright held by the author.
Pharmaceutical sciences
Biochemistry
Chemistry
biologics
claMP Tag
molecular probe
proteolysis
Development of Biologics Using the claMP Tag: Influence of the claMP Tag on Half-life and Proteolytic Stability
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25385/1/McNiff_ku_0099D_15401_DATA_1.pdf
File
MD5
da122b9f78e4aaf14e97c505281fd9fe
9908351
application/pdf
McNiff_ku_0099D_15401_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25385/2/McNiff_ku_0099D_15401_DATA_1.pdf.txt
File
MD5
af4ed430241cbeba545c39b71e7d4d65
264044
text/plain
McNiff_ku_0099D_15401_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/106892020-09-01T14:04:26Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Laird
author
Bagby, Taryn Rochelle
cmtemember
Berkland, Cory J.
cmtemember
Krise, Jeffrey P.
cmtemember
Stella, Valentino J.
cmtemember
Yang, Xinmai
2013-01-20T17:49:04Z
2013-01-20T17:49:04Z
2011-12-31
http://dissertations.umi.com/ku:11934
http://hdl.handle.net/1808/10689
Many cancers, including melanoma and breast cancer, metastasize via the lymphatic system, a mono-directional network of vessels and nodes that parallels the circulatory system. Accurate determination of the lymph nodes involved in the early lymphatic spread of the primary tumor is paramount for survival of the patient. Melanoma and breast cancer, when detected early offer promising 5-year survival rates of more than 90%; however, once the metastases have spread beyond the lymph node basin draining the primary tumor, the typical first metastatic site, to successive lymph nodes or organs, the 5-year survival dramatically drops to less than 20%. However, conventional systemic chemotherapy offers limited penetration into the lymphatic to treat lymphatic metastases, and often the dose limiting toxicities associated with systemic chemotherapy limit the dose to below that needed for effective treatment. Therefore, there is a great need to develop localized treatment and imaging agents for the delivery and identification of the tumor lymphatics and metastases, which can offer enhanced detection and improved efficacy and reduced toxicity over systemic therapy. Specific targeting of the lymphatics is possible by utilizing the natural structure of the lymphatic capillaries by tailoring the size and charge of the carriers to 10 to 100 nm in diameter and modifying the surface charge to be neutral to anionic in nature. Herein this dissertation focuses on the development and optimization of two different polymeric platforms for enhanced lymphatic uptake by tailoring the size and degree of anionic charge, utilizing hyaluronan and star polymers, respectively, as intralymphatic delivery platforms for the use in imaging and treatment of lymphatically metastatic cancers, such as melanoma and breast cancer. Further, the development of a geldanamycin-polymer conjugate utilizing the optimized star polymer and evaluation of its efficacy in three orthotopic tumor models for melanoma and breast cancer will also be discussed.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Breast cancer
Drug delivery
Imaging
Lymphatic
Melanoma
Star polymer
Development and Optimization of Polymeric Carriers for Lymphatic Imaging and Drug Delivery
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/10689/1/Bagby_ku_0099D_11934_DATA_1.pdf
File
MD5
bdd9409c6ec019e53ca916ed15ae1c33
33606385
application/pdf
Bagby_ku_0099D_11934_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10689/2/Bagby_ku_0099D_11934_DATA_1.pdf.txt
File
MD5
bcec57933a2055c3477f935086438443
300408
text/plain
Bagby_ku_0099D_11934_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/114692020-09-29T13:59:34Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Munson, Eric J.
author
Pyszczynski, Sarah Jane
cmtemember
Laurence, Jennifer S.
cmtemember
Lunte, Susan M.
cmtemember
Wang, Michael
cmtemember
Carlson, Robert G.
2013-07-14T15:49:16Z
2013-07-14T15:49:16Z
2013-05-31
http://dissertations.umi.com/ku:12809
http://hdl.handle.net/1808/11469
Trehalose has many applications as an excipient in pharmaceutical formulations; however, its use is limited in part because the transformations among the solid forms of trehalose are not yet understood. Form changes that occur during manufacturing or storage of a pharmaceutical formulation can be detrimental to the stability of a drug product, and therefore, understanding the solid-state transformations of trehalose is critical to its increased use in the pharmaceutical industry. In this dissertation, the solid forms of trehalose and the transformations among them are investigated using a variety of techniques, most importantly, differential scanning calorimetry (DSC) and 13C solid-state NMR spectroscopy (SSNMR). Currently, trehalose is thought to exist in four solid forms: a crystalline dihydrate (Th), the β-anhydrate (Tβ), the α-anhydrate (Tα), and the amorphous form (Tam). Using SSNMR, we showed that there is a fifth solid form (Tδ) that is formed when Th is dehydrated at or below 100 ºC. This form is metastable, and like Tα, it rapidly reverts to Th upon exposure to ambient conditions. Tδ was not detected using powder X-ray diffraction (PXRD), often considered the "gold standard" for polymorph identification, demonstrating the utility of SSNMR in analyzing pharmaceutically relevant systems. There is significant confusion in the literature regarding which anhydrous forms of trehalose are generated when Th is dehydrated, and we have demonstrated that source variability and lot-to-lot variability of Th is a likely source of this confusion. Using DSC, we showed that when sieved Th is heated at 10 ºC/minute, three distinct behaviors are observed: 1) the sample will dehydrate to form Tβ directly, 2) the sample will dehydrate to form Tam which crystallizes to Tβ upon further heating, or 3) the sample will dehydrate to form Tam that remains amorphous. The DSC results were used to develop a classification system that can be used to predict the products of dehydration of Th under various conditions. SSNMR was also used to analyze Tam prepared via lyophilization and dehydration of Th, and the results indicate that the subtle structural differences between the samples are not consistent with polyamorphism. However, lyophilized Tam appears to be more homogeneous and at a higher energy state than dehydrated Tam. A SSNMR subtraction method was developed in order to determine if low levels of Tβ or Tβ nuclei are present in Tam samples, and for several samples with higher tendencies to crystallize to Tβ, peaks corresponding to Tβ were detected. The greater understanding of the solid forms of trehalose that was achieved during the experiments described in this dissertation will: 1. Allow materials scientist to explicitly define the relationships among the solid forms of trehalose. 2. Assist pharmaceutical scientists in the development of more stable formulations that contain trehalose. 3. Aid biologists in determining the mechanism by which trehalose stabilizes biomolecules.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Differential scanning calorimetry
Solid-state nmr
Solid-state transformations
Trehalose
Understanding Transformations of Trehalose in the Solid State
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/11469/1/Pyszczynski_ku_0099D_12809_DATA_1.pdf
File
MD5
1eaead5828af8bdd2967b4b440408473
45244206
application/pdf
Pyszczynski_ku_0099D_12809_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/11469/2/Pyszczynski_ku_0099D_12809_DATA_1.pdf.txt
File
MD5
f68b17943f8ab5e78587b17711a62e69
377370
text/plain
Pyszczynski_ku_0099D_12809_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253892021-10-28T19:38:37Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Tolbert, Thomas J
author
Shah, Ishan Sanjeev
cmtemember
Volkin, David B
cmtemember
Schöneich, Christian
cmtemember
Wang, Michael
cmtemember
Deeds, Eric
2017-11-16T04:15:55Z
2017-11-16T04:15:55Z
2017-08-31
http://dissertations.umi.com/ku:15485
http://hdl.handle.net/1808/25389
Therapeutic monoclonal antibodies based on the IgG class of antibodies are glycoproteins that contain glycosylation sites within their Fc region. Glycosylation is important for Fc-mediated effector functions such as Antibody Dependent Cellular Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC). IgG has four subclasses: IgG1, IgG2, IgG3 and IgG4. All IgG subclasses contain a consensus glycosylation site in the CH2 domain at N297, and glycosylation at that site is considered essential for optimal Fc function and stability. IgG3 is the only subclass that has an additional glycosylation site in the CH3 domain at N392. This site has nearly gone unmentioned and was only recently shown to be partially glycosylated in serum IgG3; however, the biological role of N392 glycosylation remains uninvestigated in the literature. The primary focus of this dissertation work is to study the effect of N-glycosylation on Fc receptor interactions, structure and physical stability of IgG3. LC-MS based glycopeptide mapping studies revealed that the N392 site is partially glycosylated in human serum IgG3 and the glycans at the N392 site showed significant differences compared to the N297 site in levels of core fucosylation, bisecting GlcNAc and mannosylation. The presence of glycosylation at the N392 site in the naturally occurring IgG3 establishes its biological relevance and makes a case for its characterization. For structural and biochemical characterization studies, the Fc fragment of IgG3 was expressed in a glycosylation-deficient strain of the yeast Pichia pastoris. Two variants of IgG3 Fc were produced, one with both sites glycosylated and another with only the N297 site glycosylated. These two forms were compared to investigate the effect of N392 glycosylation on the Fc receptor binding activity and physical stability of IgG3 Fc. Our results indicate that presence of the additional N392 glycan does not affect the binding of IgG3 Fc with the FcRIIIA and FcRn receptors but does affect the conformational stability and aggregation propensity of IgG3 Fc. Additionally, crystal structures of both the IgG3 Fc variants were determined with a resolution of 1.8-2.0 Å and were compared with the published structures of Fc fragments from the other IgG subclasses. Structural analysis of key amino acid differences between IgG3 and other IgG subclasses provided insight into IgG3-specific properties, especially related to binding with protein A, protein G, and the FcRn receptor. The importance of N297 glycans for IgG3 Fc- FcRIIIA interaction was also demonstrated from a structural perspective. The location and orientation of the N392 glycans in the IgG3 Fc structure provided a probable explanation for the observed effect of these glycans on Fc receptor binding activity and physical stability of IgG3 Fc.
en
Copyright held by the author.
Pharmaceutical sciences
alpha 1
2 mannosidase
Fc gamma receptor
FcRn
Man5
Pichia pastoris
X-ray crystal structure
SITE-SPECIFIC GLYCOSYLATION ANALYSIS OF IgG3 AND THE EFFECT OF GLYCOSYLATION ON THE STRUCTURE, PHYSICAL STABILITY AND Fc RECEPTOR INTERACTIONS OF IgG3 Fc
Dissertation
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URL
https://kuscholarworks.ku.edu/bitstream/1808/25389/1/Shah_ku_0099D_15485_DATA_1.pdf
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oai:kuscholarworks.ku.edu:1808/39722020-07-16T14:18:54Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Audus, Kenneth L
author
Desino, Kelly Elizabeth
cmtemember
Borchardt, Ronald T
cmtemember
Siahaan, Teruna J.
cmtemember
Lunte, Susan M.
cmtemember
Michaelis, Mary Lou
2008-07-21T22:50:44Z
2008-07-21T22:50:44Z
2008-05-06
http://dissertations.umi.com/ku:2516
http://hdl.handle.net/1808/3972
The blood brain barrier is the body's natural defense system for limiting the brain's exposure to potentially harmful xenobiotics. This barrier exists between the blood of the systemic circulation and the brain and is made up of brain endothelial cells which have tight junctions, reduced pinocytosis, minimal fenestration and increased expression of metabolizing enzymes and membrane transporters capable of efflux. Estimates predict that the blood brain barrier may be capable of limiting up to 98% of all drugs from entering the brain and is therefore a major obstacle in drug delivery. The research presented herein highlights several small molecules that possess chemotherapeutic and neuroprotective properties. These molecules also represent various strategies for improving blood brain barrier penetration. Derivatives of the microtubule stabilizing agent paclitaxel were investigated in which chemical modification was employed to reduce interaction with the efflux transporter P-glycoprotein, which is critical in limiting paclitaxel's entry into the brain. TH-237A, another microtubule stabilizing agent that is structurally very different from paclitaxel was also characterized and was shown to have excellent blood brain barrier penetration. Additionally, derivatives of the monoamine oxidase inhibitor tranylcypromine were explored that have fatty acid and lipoamino acid chains of varying length attached to improve blood brain barrier permeability. In order for these compounds to exert their mechanism of action as either chemotherapeutic or neuroprotective agents, they must be able to penetrate the blood brain barrier. The specific objective of this project was to explore various chemical approaches to improving blood brain barrier permeability using pharmacologically relevant molecules.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Blood-brain barrier
Neuroprotection
P-glycoprotein
Paclitaxel
Bbmec
Improving Blood Brain Barrier Permeation of Small Molecules Exhibiting Chemotherapeutic and Neuroprotective Effects
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/3972/1/umi-ku-2516_1.pdf
File
MD5
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umi-ku-2516_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/3972/2/umi-ku-2516_1.pdf.txt
File
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umi-ku-2516_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216252020-10-16T14:24:55Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Middaugh, Russ
author
Gleason, Camille
cmtemember
Volkin, David
cmtemember
Yee, Chanel k
2016-10-11T15:18:25Z
2016-10-11T15:18:25Z
2013-12-31
http://dissertations.umi.com/ku:13117
http://hdl.handle.net/1808/21625
Shear thinning behavior, observed in shear viscosity tests of IgG therapeutic molecules, may lead to inaccurate reporting of apparent viscosity, depending on the severity of the shear thinning behavior. To determine whether shear thinning is an intrinsic bulk property or an interfacial phenomenon, shear thinning behavior was tested as a function of bulk concentration with IgG1 and IgG2 molecules. Indeed if shear thinning is a bulk property, then the higher the concentration, the greater the shear thinning effect. The 70 mg/ml and 0.007 mg/ml samples showed the least shear thinning in comparison to 0.7 mg/ml concentrations of both the IgG1 and IgG2 molecules. This suggests that high bulk concentration did not produce the greatest shear thinning effects; therefore bulk properties do not contribute to the shear thinning effect. To test the sensitivity of the IgG molecules at the air-water interface, the surface area to volume ratio (SA:V) of samples exposed to the air-water interface were varied by the measuring system. The measuring systems used were: Cone and Plate 25 mm (CP 25), Cone and Plate 50 mm (CP 50) and Double Gap (DG). Their respective SA:V exposed to air were: 155 m-1, 108 m-1, and 33 m-1 with an Anton Paar MCR 302 rheometer. For both IgG1 and IgG2 molecules, the measuring systems with the highest SA:V ratios produced the most dramatic shear thinning effects. IgG1 molecules were more sensitive to changes in SA:V but IgG2 molecules showed higher magnitude shear thinning effects. To further probe the behavior of the IgG molecules at the air-water interface, interfacial oscillatory rheology with a Bicone (BC) was performed at a constant stress and strain (1 Hz, 1 %). The IgG molecules showed solid behavior (G'i) at 0.7 mg/ml over a 22 hour period. At 70 mg/ml and 0.007 mg/ml, liquid behavior (G''i) was dominant for both molecules. In fact, at 70 mg/ml G'i was not detected by the rheometer. Furthermore, the addition of polysorbate 20 (PS20) minimized shear thinning behavior as well as G'i. IgG1 had a G'i/G''i crossover point over half an hour after testing while IgG2 had a crossover point seconds into the test. This suggests different film formation behavior for IgG1 and IgG2. The slow continuous growth of G'i over 22 hours suggests the formation of multi-layer's of mAbs beneath the air-water interfacial monolayer.[4] To orthogonally verify the presence of IgG molecules at the air-water interface, interfacial tension (IFT) was also measured at the 0.7 mg/ml IgG molecule concentrations and in the respective IgG buffers. For both IgG molecules, IFT was reduced relative to the buffers.
en
Copyright held by the author.
Pharmaceutical sciences
air-water interface
immunoglobulin
interfacial rheology
rheology
shear-thining
viscosity
Probing Shear Thinning Effects on IgG Molecules at the Air-water Interface via Viscosity and Rheological Measurements
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21625/1/Gleason_ku_0099M_13117_DATA_1.pdf
File
MD5
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application/pdf
Gleason_ku_0099M_13117_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21625/2/Gleason_ku_0099M_13117_DATA_1.pdf.txt
File
MD5
3845fec12bedf6bb1f9719d7e30b197a
75965
text/plain
Gleason_ku_0099M_13117_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/102112018-01-31T20:08:05Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Berkland, Cory J.
author
Alghaith, Adel Faleh
cmtemember
Forrest, Laird
cmtemember
Volkin, David B.
2012-10-27T10:34:56Z
2012-10-27T10:34:56Z
2012-08-31
http://dissertations.umi.com/ku:12309
http://hdl.handle.net/1808/10211
Proteins and peptides have been increasingly used to treat many diseases including autoimmune diseases and cancer. The benefits of using peptides and proteins as drugs for treatment are higher target specificity and pharmacological potency when compared to traditional small molecule drugs. However, the instability and immunogenicity of peptides and proteins can limit their translation as therapeutics. Several strategies have been used to improve the physical and chemical stability of peptides and proteins or to extend the half-life in vivo such as modification of N- and C-terminus, PEGylation and cyclization. In addition, glycosylation is a post-traditional modification that can improve the stability of peptides and proteins. Current approaches for synthetic glycosylation often use multiple steps, such as chemical modification of the glycans to form reactive compounds, protection of reactive groups that give undesirable products, using glycosyltransferases to transfer saccharide moieties to peptides and installation of linker molecules to improve reaction efficiency. Two different peptides, aminooxy-proteolipid peptide (AoPLP), and proteolipid peptide (PLP, a known antigen in multiple sclerosis) have been used in this report. A single-step glycosylation in aqueous buffer was achieved by reacting an aminooxy peptide to N-acetyl glucosamine. A series of control experiments suggested that the product formed due to the reaction of the terminal aminooxy group on the peptide with the aldehyde group that is produced from the ring opening of NAG.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
A Single-step Reaction for Glycosylation of Aminooxy Peptides
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/10211/1/Alghaith_ku_0099M_12309_DATA_1.pdf
File
MD5
aa039ccfd57b0c09a97b83178c76a716
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Alghaith_ku_0099M_12309_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10211/2/Alghaith_ku_0099M_12309_DATA_1.pdf.txt
File
MD5
0ebe2f97d5df3ec4526ddb9e9f10e5be
45681
text/plain
Alghaith_ku_0099M_12309_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/121872020-10-08T14:27:53Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John F.
author
Voth, Laura Marie
cmtemember
Forrest, Laird
cmtemember
Searles, Jim
2013-09-29T14:10:33Z
2013-09-29T14:10:33Z
2013-08-31
http://dissertations.umi.com/ku:12959
http://hdl.handle.net/1808/12187
In the pharmaceutical industry, the success of a new drug product is strongly impacted by the stability of the drug formulation. For many formulations, stability is governed by the drug product's water content, thus the ability to regulate this content determines the viability as a commercial product. Through lyophilization, the water content of a drug product may be controlled at the time of manufacture. However, over the product shelf life, additional water may be added or removed due to factors such as the storage environment and the drug's container/closure system, typically a vial, stopper, and cap. The water present in the rubber stopper may interact with the vial contents, potentially influencing the drug product's stability. Consequently, a formulation scientist must establish test methods capable of determining the initial and potentially subsequently changing moisture content for not only the lyophilized cake, but also the stopper. Current literature describes two main analytical methods for measurement of the water content of rubber stoppers: a gravimetric method and a Karl Fischer (KF) titration method with oven. A third less common test method is the Karl Fischer titration method with tetrahydrofuran (THF) extraction. The results presented in this thesis thus describe the evaluation of the KF titration method utilizing an oven and the KF titration method utilizing a THF solvent extraction. The critical parameters of each test method were examined, and the advantages and disadvantages of these analytical methods were identified. Ultimately, it was concluded the drug product manufacturer must determine, based on knowledge of the drug product integrity and available manufacturing processes, the extent to which the water content of the rubber stoppers must be quantified, as well as define the test method to be employed to perform this moisture content measurement.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Drug stability
Elastomer
Fischer, Karl
Lyophilization
Rubber stopper
Water content
Water Content Determination of Rubber Stoppers Utilized for Sealing Lyophilized Pharmaceutical Products: Assessment of Two Karl Fischer Titration Methods
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/12187/1/Voth_ku_0099M_12959_DATA_1.pdf
File
MD5
51ff8ca7f7f21623c4a1eace4364c11e
3944009
application/pdf
Voth_ku_0099M_12959_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/12187/2/Voth_ku_0099M_12959_DATA_1.pdf.txt
File
MD5
527b55d825d60d9b325f6b2a53ee3fc1
189099
text/plain
Voth_ku_0099M_12959_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216312020-10-16T14:45:24Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Forrest, Marcus L.
author
Zhao, Yunqi
cmtemember
Berkland, Cory J.
cmtemember
Krise, Jeffrey P.
cmtemember
Wang, Zhuo
cmtemember
Yang, Xinmai
2016-10-11T15:43:54Z
2016-10-11T15:43:54Z
2013-12-31
http://dissertations.umi.com/ku:13183
http://hdl.handle.net/1808/21631
Formulation issues, including stability, solubility and bioavailability, have been identified as key concerns in anti-cancer drug development. The challenges in pharmaceutical formulation often arise from the different physicochemical attributes of a molecule and the need to deliver the compound to a desired site. The major problems of small molecule drug formulation development are poor water solubility and off target toxicity. In chapter 2 of this dissertation, a prostate specific membrane antigen (PSMA) targeted micelle was made to deliver a PI3K inhibitor, TGX-221, for prostate cancer treatment. The in vitro cell culture based study indicated that the targeted micelle significantly improved cellular uptake by PSMA positive cells. The in vivo animal efficacy study showed that the targeted micelle significantly reduced tumor size and progression in a xenograft model. Ridaforolimus, a non-prodrug rapamycin analog, has entered clinical trials for cancer treatment. Formulations of ridaforolimus being evaluated in the clinical trials include intravenous infusion and oral administration. The intravenous bolus formulation of this drug is very limited due to poor water solubility (ca. 200 µg/mL). In chapter 3, we showed that a new formulation of ridaforolimus using DSPE-PEG2000 micelle as a carrier greatly improved the drug solubility, increasing it 40 times. In addition, the pharmacokinetic properties examined in rats showed that this formulation significantly increased drug retention in the plasma. In chapter 4, a hyaluronic acid-rapamycin conjugate was synthesized and characterized. The disposition and efficacy of the drug conjugate were studied and demonstrated that the hyaluronic acid drug conjugate could be used for treating localized CD44 positive cancer. In chapter 5, a doxorubicin prodrug was developed for enhancing oral bioavailability. Doxorubicin was chemically conjugated with quercetin, a flavonoid, via a glycine linker. Quercetin is a P-glycoprotein inhibitor; thus, it prevents doxorubicin efflux by this mechanism. The oral bioavailability of DOX was significantly improved in rats through this prodrug strategy. In the last chapter, an HPLC method was developed for the separation of active compounds from degraded alternol, which could be used for alternol manufacturing and stability studies.
en
Copyright held by the author.
Pharmaceutical sciences
anti-cancer drug
formulation development
small molecules
Formulation Development of Anti-Cancer Drugs
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21631/1/ZHAO_ku_0099D_13183_DATA_1.pdf
File
MD5
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ZHAO_ku_0099D_13183_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21631/2/ZHAO_ku_0099D_13183_DATA_1.pdf.txt
File
MD5
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text/plain
ZHAO_ku_0099D_13183_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216642018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Tolbert, Thomas J
author
Hutchison, Kevin Michael
cmtemember
Siahaan, Teruna J
cmtemember
Wang, Zhuo
2016-10-11T19:16:56Z
2016-10-11T19:16:56Z
2015-12-31
http://dissertations.umi.com/ku:14300
http://hdl.handle.net/1808/21664
Interleukin 1 (IL-1) is an inflammatory cytokine that helps the immune system fight disease. The inflammatory action of IL-1 is regulated by the naturally occurring interleukin 1 receptor antagonist (IL-1ra). IL-1ra contains one N-linked glycosylation site and is expressed in humans in both glycosylated and non-glycosylated forms. The one current IL-1ra drug available (Kineret®) is expressed in Escherichia coli as a non-glycosylated form. Because of this, most studies of IL-1ra have been done with the non-glycosylated form and the effects of glycosylation have not been studied. This research attempts to study the effects of the glycosylation of IL-1ra with its binding to the interleukin 1 receptor type 1 (IL-1R1). Both IL-1R1 and IL-1ra were expressed in a glycosylation deficient strain of Pichia pastoris. In-vitro binding experiments between the two proteins were studied using both biolayer interferometry and size exclusion chromatography. Due to the long dissociation rate between IL-1ra and IL-1R1, biolayer interferometry was an unfeasible method. Size exclusion chromatography, however, proved to be a promising tool to study binding. Initial experiments with non-glycosylated IL-1ra showed a potential KD of 1.7 nM. Future studies need to be done using the glycosylated form of IL-1ra to determine any differences in binding between the glycosylated form and the non-glycosylated form.
en
Copyright held by the author.
Pharmaceutical sciences
Role of Glycosylation of IL-1ra on its Binding to IL-1R1
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21664/1/Hutchison_ku_0099M_14300_DATA_1.pdf
File
MD5
c8225ee92854ccdface655ec5217c7c1
1645815
application/pdf
Hutchison_ku_0099M_14300_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21664/2/Hutchison_ku_0099M_14300_DATA_1.pdf.txt
File
MD5
768a459674a7c0dc8b4d73d90516fc68
74229
text/plain
Hutchison_ku_0099M_14300_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/76432020-08-10T14:23:56Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Stella, Valentino J.
advisor
Munson, Eric J.
author
Gorman, Eric M.
cmtemember
Laurence, Jennifer S.
cmtemember
Berkland, Cory J.
cmtemember
Dunn, Robert C.
2011-06-21T16:34:00Z
2011-06-21T16:34:00Z
2011-03-25
http://dissertations.umi.com/ku:11329
http://hdl.handle.net/1808/7643
The majority of pharmaceutical dosage forms are marketed as solids, and the active pharmaceutical ingredient (API) can exist in various physical forms. These physical forms can be either crystalline or amorphous, and will have different physical properties. The physical form of the API is selected to provide the appropriate solubility, stability, and bioavailability for the formulation. However, processing steps involved in the production of the formulation can induce changes in the physical form of the API and thus impact the performance of the formulation. Therefore, it is critical to characterize the physical form of the API in the formulation, and to monitor it for any changes in the physical form during storage. Multiple solid-state characterization techniques are typically employed in order to identify and quantitate physical forms of APIs. However, most of these techniques suffer from significant issues related to the interference of excipient signals with API signals when analyzing formulations. Additionally, in order to perform quantitative measurements pure standards are needed and calibration curves must be generated for most of these characterization techniques. This dissertation demonstrates the superior ability of solid-state nuclear magnetic resonance (SSNMR) spectroscopy to both detect and quantitate physical forms of APIs within formulations, relative to other solid-state characterization techniques. Specifically, SSNMR has been used to understand the dehydration of levofloxacin hemihydrate, including the discovery of a previously unreported anhydrous polymorph. Three formulations for pulmonary delivery have been characterized by both differential scanning calorimetry (DSC) and SSNMR. DSC could not clearly identify the physical form of the APIs in the formulations, but SSNMR was able to unambiguously determine the physical forms of the APIs in all cases. The work presented in the dissertation also demonstrates that SSNMR can be used to quantitate the relative amounts of physical forms of APIs within formulations without pure standards or calibration curves. Finally, the relative ability of SSNMR and other solid-state characterization techniques were compared and clearly illustrate that SSNMR is considerably more powerful in the relative quantitation of API physical form in both pure materials and formulations.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Analytical chemistry
Active pharmaceutical ingredient (api)
Amorphous
Crystalline
Formulation
Quantitation
Solid-state nmr
Solid-State Physical Form Detection and Quantitation of Pharmaceuticals in Formulations
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/7643/1/Gorman_ku_0099D_11329_DATA_1.pdf
File
MD5
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Gorman_ku_0099D_11329_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/7643/2/Gorman_ku_0099D_11329_DATA_1.pdf.txt
File
MD5
083a57cc3bd10f57669804f85596a2de
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text/plain
Gorman_ku_0099D_11329_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/104102018-11-15T16:38:32Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Forrest, Laird
author
Alhowyan, Adel Ali B.
cmtemember
Krise, Jeffrey P.
cmtemember
Siahaan, Teruna J.
2012-11-20T00:09:41Z
2012-11-20T00:09:41Z
2012-08-31
http://dissertations.umi.com/ku:12332
http://hdl.handle.net/1808/10410
The purpose of this study was to determine the mechanism of uptake and release of doxorubicin from HA nanoparticle. We used human head and neck squamous cell carcinoma MDA-1986 as a model cell line. MDA-1986 was imaged after incubation with HA-DOX (NPs), doxorubicin, HA-CY7 or HA-DOX-CY7 at 15 minutes, 1, 6, 24, and 48 hours' time points using an inverted fluorescence microscope. Also, the cell nucleus was stained with DAPI stain, and the cells were imaged after incubation with HA-DOX conjugates, doxorubicin, HA-CY7 or HA-DOX-CY7 for 6 hours. Furthermore, the lysosomes were stained to determine if the lysosomal pathway is the major degradation pathway of the nanoparticles and the carrier. To determine the internalization mechanism, four inhibition conditions were used: excess HA to block HA receptors, anti CD44 antibody (Hermes-1) to block the CD44 receptor, chlorpromazine to inhibit clathrin mediated endocytosis, and reduced temperature of 4°C. The fluorescence intensities of the cells co-incubated with the nanoparticle or the carrier with different inhibitors were compared using the inverted fluorescence microscope. The quantitative analysis of cells treated with HA-DOX and co-incubated with different inhibition conditions (10 mg/mL HA, chlorpromazine, Hermes-1 and 4°C) showed significant decrease in the fluorescence intensity except in cells pretreated with 5 mg/mL HA. Also, the quantitative analysis of cells treated with HA-CY7 and co-incubated with different inhibition conditions (excess HA, chlorpromazine and Hermes-1) showed significant decrease in the fluorescence intensity. However, the quantitative analysis of cells treated with free doxorubicin or HA-DOX-CY7 showed significant decrease in the fluorescence intensity in only cells pretreated with 25- µM chlorpromazine or cells incubated at 4 °C. The suggested internalization mechanism of HA-DOX conjugates is an active transport mechanism mediated mainly by the CD44, one of the HA receptors, through a clathrin-dependent endocytic pathway. On the other hand, a sulfated-HA derivative has similar uptake profile as the parent HA-CY7, and it is mainly localized in the cytosol.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Intracellular Trafficking and Uptake of Hyaluronan-Doxorubicin Conjugates in Vitro
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/10410/1/ALHOWYAN_ku_0099M_12332_DATA_1.pdf
File
MD5
2f6f7755c1175d1c82e15170d9b4e0a5
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application/pdf
ALHOWYAN_ku_0099M_12332_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10410/2/ALHOWYAN_ku_0099M_12332_DATA_1.pdf.txt
File
MD5
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ALHOWYAN_ku_0099M_12332_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/225132018-07-24T17:58:19Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Lunte, Susan M
author
Creamer, Jessica Stephens
cmtemember
Nordheden, Karen J
cmtemember
Siahaan, Teruna J
cmtemember
Stobaugh, John F
cmtemember
Wang, Micheal Z
2017-01-08T18:34:37Z
2017-01-08T18:34:37Z
2014-08-31
http://dissertations.umi.com/ku:13608
http://hdl.handle.net/1808/22513
https://orcid.org/0000-0003-2890-4901
Maintaining a consistent supply of pharmaceuticals to developing countries could save millions of lives per year. One of the major roadblocks in this effort is an abundance of substandard and counterfeit drugs in the supply chain. To prevent these products from being distributed, improved methodology and instrumentation for drug screening is needed. In these low-resource areas the availability of proper funding and laboratory space is limited. To replace the expensive liquid chromatography and mass spectrometry instrumentation traditionally used for quality control, capillary electrophoresis (CE) can be used. CE has a low startup cost and, because of the small sample and reagent volume requirements, the cost per test is kept to a minimum. Additionally, any methodology developed for CE can be transferred to the miniaturized platform of microchip electrophoresis (ME). ME further reduces the cost-per-test and provides the potential for a fully portable analytical device that can be used for on-site analysis. This method is particularly useful for screening pharmaceuticals throughout the many distribution lines, store houses, and clinics across a large country. In this dissertation, CE was used to develop methodology for the analysis of the peptide drug oxytocin (OT). OT is needed in developing countries to prevent death from post-partum hemorrhage. A major concern regarding the supply chain of peptide-based drugs is the degradation of these products when then are shipped and stored incorrectly. Several degradation products are produced when OT is subjected to heat-stress conditions. Deamidation, in particular, produces small molecular changes that have significant effects on the biological activity of the peptide. Initially, methodology for the separation and detection of desamino degradation products of OT was developed for CE-UV. OT contains three potential sites of deamidation, which leads to seven distinct desamino products. The separation was achieved following an optimization of the background electrolyte to include a pseudostationary phase and an organic modifier to increase selectivity and resolve the eight structurally similar peptides. To improve the functionality of the CE assay for OT integrity screening, the next step of was to further optimize the method for a separation of all of the known degradation products formed under heat-stressed OT formulations. However, current literature on the degradation of OT does not yet addressed the degradation of Pitocin pharmaceutical formulations that are prepared in water containing a small amount of acetic acid, to adjust the pH between 3-5, and 0.5% chlorobutanol as a preservative. To investigate the effect that CB and CB-like products have on the degradation of OT, LC-UV-MS was used to monitor the formation of degradation products as a function of time. The preliminary data shows that CB, and the structurally similar trichloroethanol (TCE), significantly stabilize OT from the heat-stress degradation. The addition of either of these trichloro species substantially reduces the rate of degradation observed over a 48 h period at 70 °C. Further work is needed on this project to determine the cause of this protective effect by performing structural studies of OT in the presence of CB or TCE. Finally, initial steps were taken towards the development of a low-cost portable ME device. A significant percentage of small molecule counterfeit drugs are formulated with the wrong amount of active ingredient. Current portable analytical methods available to monitor the pharmaceutical supply chain are limited in their quantitative abilities. By coupling ME to conductivity detection, it is possible to perform quantitative analysis of multiple species simultaneously. Initial experiments to evaluate system performance were performed using two first-line anti-tuberculosis drugs, ethambutol and isoniazid.
en
Copyright held by the author.
Analytical chemistry
Biotechnology
Capillary electrophoresis
Developing countries
Microchip electrophoresis
Pharmaceutical analysis
Protein therapeutic
The Development of Capillary and Microchip Electrophoresis Methods for the Analysis of Pharmaceuticals in Developing Countries
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/22513/1/Creamer_ku_0099D_13608_DATA_1.pdf
File
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Creamer_ku_0099D_13608_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/22513/2/Creamer_ku_0099D_13608_DATA_1.pdf.txt
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9b5a6662fd7f2888157d94f43d559c34
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Creamer_ku_0099D_13608_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/76472020-08-07T14:36:10Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John F.
author
Calahan, Julie L.
cmtemember
Munson, Eric J.
cmtemember
Alvarez-Nunez, Fernando
2011-06-21T16:41:44Z
2011-06-21T16:41:44Z
2011-04-26
http://dissertations.umi.com/ku:11487
http://hdl.handle.net/1808/7647
Purpose. Recently there has been increasing interest in the development of amorphous materials, particularly on developing low solubility drugs as amorphous solid dispersions (ASDs). Understanding the crystallization rate of miscible and partially miscible ASDs is critical for the development of amorphous drugs as solid dispersions. This project focuses on examining the solid state properties of AMG 517 in HPMC-AS polymer, and stability using isothermal microcalorimetry and SSNMR. Methods. ASDs of AMG 517 in HPMC-AS were manufactured using a Buchi 290 Mini Spray Dry system. Several techniques were used to evaluate the ASDs, including XRPD, GC, TGA, mDSC, SEM and vapor sorption. Crystallization of ASDs at elevated conditions of temperature and humidity were evaluated using isothermal microcalorimetry (TAM). Crystallinity was measured using 19F SSNMR. Results. XRPD and mDSC evaluations demonstrated that all manufactured ASDs were amorphous. Although residual solvent contributes to the depression of Tg values of ASDs in general, significant depression of the Tg is observed which is not accounted for by residual solvent effects. Crystallization events for AMG 517 in HPMC-AS at temperature and relative humidity conditions near the Tg were observed by TAM, as long as heat flow is >1ìW. At conditions below the T1ìW. At conditions below the Tg, crystallization is much slower, resulting in heat signal so low that it is difficult to identify a single crystallization event. However, SS-NMR confirms partial crystallization of HPMC-AS ASDs even for slow crystallizations below Tg. A dual mechanism was observed for crystallization of some ASDs indicating possible phase separation at higher drug loads, which was not observed by mDSC. Conclusions. Isothermal microcalorimetry can provide important kinetic data for the crystallization of ASDs. The crystallization of ASDs of AMG 517 in HPMC-AS follows the expected trends in terms of temperature and humidity (i.e. faster crystallization at higher temperature and humidity conditions). Crystallization is significantly slowed by the presence of HPMC-AS polymer. Rate constants for ASD crystallizations aid drug load selection for maximizing stability while minimizing polymer in the formulation.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
19f ssnmr
Amorphous solid dispersions
Glass transition
Hpmc-as
Isothermal microcalorimetry
Solid state kinetics
Characterization of Amorphous Solid Dispersions of AMG 517 in HPMC-AS and Crystallization using Isothermal Microcalorimetry
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/7647/1/Calahan_ku_0099M_11487_DATA_1.pdf
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Calahan_ku_0099M_11487_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/7647/2/Calahan_ku_0099M_11487_DATA_1.pdf.txt
File
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Calahan_ku_0099M_11487_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/97362020-09-01T13:45:46Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Siahaan, Teruna J.
author
Badawi, Ahmed H.
cmtemember
Berkland, Cory J.
cmtemember
Krise, Jeffrey P.
cmtemember
Volkin, David B.
cmtemember
Kuczera, Krzysztof
2012-06-03T14:32:04Z
2012-06-03T14:32:04Z
2011-12-31
http://dissertations.umi.com/ku:11923
http://hdl.handle.net/1808/9736
Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human disease multiple sclerosis (MS). In EAE and MS, the immune system recognizes proteins of the myelin sheath as antigenic, and an inflammatory reaction is initiated within the central nervous system (CNS), leading to demyelination of the axons. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. The objective of this project is to develop peptides that target myelin-specific antigen presenting cells (APC) in order to modulate the immune response towards the myelin sheath. Bifunctional peptide inhibitors (BPI) are molecules composed of an antigenic peptide and an adhesion peptide that are designed to target the major histocompatibility class-II molecule and adhesion receptors, respectively, on the surface of APC. The simultaneous binding to both receptors on the APC is proposed to hinder the delivery of activation signals to T cells and, therefore, attenuate the inflammatory T cell response. In this study, PLP-BPI, a well-studied BPI molecule, was tested as a peptide vaccine in preventing the onset of EAE as well as for its role in providing protection against blood-brain barrier breakdown during disease. Next, a novel BPI molecule known as PLP-B7AP, which targets costimulatory molecules, was developed and tested for the first time in suppressing EAE. Finally, to provide protection against the diverse pool of antigenic proteins of the myelin sheath, BPI molecules targeting other myelin antigens as well as a multivalent BPI molecule were developed. These novel peptides have consistently demonstrated a shift towards an immuno-tolerant state accompanied by significant suppression of EAE.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Development of Peptides to Target Antigen Presenting Cells for Controlling the Immune Response in Experimental Autoimmune Encephalomyelitis
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/9736/1/Badawi_ku_0099D_11923_DATA_1.pdf
File
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Badawi_ku_0099D_11923_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/9736/2/Badawi_ku_0099D_11923_DATA_1.pdf.txt
File
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oai:kuscholarworks.ku.edu:1808/278102020-10-13T19:35:01Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Forrest, Marcus L
author
Petrulis, Abigail
cmtemember
Funk, Ryan S
cmtemember
Hageman, Michael
2019-05-07T16:34:32Z
2019-05-07T16:34:32Z
2018-05-31
http://dissertations.umi.com/ku:15762
http://hdl.handle.net/1808/27810
https://orcid.org/0000-0002-8797-4072
Immunogenic cell death is a recently identified subset of apoptotic cell death that, when activated, may improve outcomes and remission rates in cancer patients. Calreticulin is an essential early-stage damage-associated molecular pattern that is triggered by certain drugs. It is thought that cancer chemotherapeutics and other agents proven to exhibit immunogenic cell death do so by creating endoplasmic reticulum stress that causes calreticulin to translocate to the cell membrane and activate more downstream signals to recruit the immune system. The current gold standard for the detection of immunogenic cell death is a lengthy and costly procedure involving immunocompetent mice vaccinated with cancer cells already exposed to the potentially immunogenic agent. This is not a realistic method to screen all agents for their potential to induce immunogenic cell death (ICD), but the only other pre-clinical models have been done in only one cancer cell line. This study aimed to generate a stable murine head and neck cancer cell line to be used for screening chemotherapeutics using fluorescence, assess the ability of these transfected cells to accurately predict ICD-inducing potential, and test newly modified chemotherapeutics for their potential to cause ICD. To do so, cells were transfected with a plasmid construct for the calreticulin protein and a red-fluorescent protein. The fluorescent model is not a replacement for the gold-standard detection of ICD, but rather enables a more high-throughput approach to the widespread testing of all clinically relevant cancer chemotherapeutics as well as specifically modified chemotherapeutics to induce ICD.
en
Copyright held by the author.
Pharmaceutical sciences
immunogenic
immunogenic cell death
niclosamide
oxaliplatin
Light It Up: A Pre-Clinical Fluorescent Model to Illustrate Immunogenic Cell Death
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/27810/1/Petrulis_ku_0099M_15762_DATA_1.pdf
File
MD5
bac00b029dc68fd34269859a88de80b7
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Petrulis_ku_0099M_15762_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/27810/2/Petrulis_ku_0099M_15762_DATA_1.pdf.txt
File
MD5
8d06062324565ce33b4c92a4bcc22179
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Petrulis_ku_0099M_15762_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/114582020-09-23T14:15:19Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Zhou, Shuxia
cmtemember
Stobaugh, John F.
cmtemember
Volkin, David B.
cmtemember
Siahaan, Teruna J.
cmtemember
Desaire, Heather
2013-07-14T15:28:34Z
2013-07-14T15:28:34Z
2012-08-31
http://dissertations.umi.com/ku:12419
http://hdl.handle.net/1808/11458
Since the approval of the first monoclonal antibody (mAb) drug in 1986, mAbs have developed into a major class of therapeutic agents due to their unique properties. Compared to traditional small molecule drug products, the actions of the antibodies are more specific leading to generally fewer off-target related side effects. Also antibodies may be conjugated to another therapeutic entity for efficient delivery of this entity to a target site, thus reducing potential side effects. On the other hand, due to the structural complexity and the dependence of stability of the antibodies on the conformation and structure, antibodies are subject to multiple degradation pathways induced by a variety of factors encountered during antibody production, purification, development, manufacturing, storage, shipping and delivery to the patients. The exposure of antibodies to redox-active metal ions and/or light during processing and use is inevitable, and may result in antibody degradation. Although abundant information on metal-catalyzed oxidation (MCO) and photo-degradation of peptides and small proteins is documented in the literature, very limited research has been performed on IgG oxidative modifications and physical instability. The research covered in this dissertation focused on two major degradation mechanisms for IgG therapeutic mAbs: chemical and physical instability induced by redox-active metal ions and photo-degradation. Redox-active metal ion-induced instability was first examined by a comprehensive study of IgG oxidation induced by MCO. The oxidation of the amino acids, especially Phe and Tyr in IgG1 was first identified, and subsequently a fluorogenic derivatization methodology was developed for their detection. Secondly, a systematic study of the conformational change and intrinsic thermal stability of IgG revealed that metal ions perturbed IgG tertiary structure resulting in decreased intrinsic thermal stability. Lastly, metal chelators were examined to protect the IgG from MCO-induced degradation. This dissertation also documents the formation of carbon-centered radicals due to homolytic cleavage of disulfide bonds upon photo-irradiation and an UPLC-MS method was developed to simultaneously separate and characterize IgG1 photo-degradants. The ultimate goal of this research is to gain better understanding of IgG degradation mechanism, thereof, providing guidance to develop a therapeutic mAb drug product with desired attributes for unmet medical needs.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Abs fluorogenic derivatization
Biophysical characterization
Igg
Mass spectrometry
Protein physical/chemical stability
Therapeutic drug product stability
Instability of Immunoglobulin G (IgG) Monoclonal Antibodies Induced by Redox-Active Metal Ions adn Photo-Irradiation
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/11458/1/Zhou_ku_0099D_12419_DATA_1.pdf
File
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Zhou_ku_0099D_12419_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/11458/2/Zhou_ku_0099D_12419_DATA_1.pdf.txt
File
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Zhou_ku_0099D_12419_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/76142019-04-12T14:43:26Zcom_1808_80com_1808_981col_1808_14157col_1808_982
KU ScholarWorks
author
Audus, Kenneth L.
author
Mitra, Pallabi
2011-06-16T16:52:34Z
2011-06-16T16:52:34Z
2010
Mitra, P. and Audus, K.L. (2010) Multidrug resistance-associated protein (MRP) isoforms and the breast cancer resistance protein (BCRP) mediate sulfate conjugate efflux out of BeWo cells. Int. J. Pharm. 384, 15-23. PMID: 19782739. http://dx.doi.org/10.1016/j.ijpharm.2009.09.033
http://hdl.handle.net/1808/7614
10.1016/j.ijpharm.2009.09.033
The breast cancer resistance protein (BCRP) and the multidrug resistance-associated proteins (MRPs) have the ability to eliminate sulfate conjugates but it is not known if this constitutes one of their roles in the placenta. To determine this, the BeWo cell line was used as a model of placental trophoblast cells and we examined the fate of two common sulfotransferase substrates, 4-nitrophenol and acetaminophen. At 0.5–200 μM, acetaminophen sulfate did not alter the accumulation of the BCRP substrates BODIPY FL prazosin or mitoxantrone in BeWo monolayers indicating a lack of interaction of BCRP with acetaminophen sulfate. 4-nitrophenyl sulfate increased the accumulation of BODIPY FL prazosin only at 200 μM, indicating it to be a BCRP inhibitor at high concentrations. Efflux studies and bidirectional transport studies examining the effect of BCRP/MRP inhibitors on the efflux of intracellularly generated 4-nitrophenyl sulfate and acetaminophen sulfate, indicated that one or more of the MRP isoforms played a major role in the elimination of 4-nitrophenyl sulfate and acetaminophen sulfate across the basolateral (fetal-facing) and apical (maternal-facing) trophoblast membranes respectively. BCRP played only a minor role in the elimination of these two sulfate conjugates across the apical membrane. Our study shows that a yet undetermined role of trophoblast efflux transporters is the elimination of sulfate conjugates
en_US
Trophoblast
Sulfate conjugate
Breast cancer resistance protein (BCRP)
Multidrug resistance-associated protein (MRP)
Mitoxantrone
BODIPY FL prazosin
Multidrug resistance-associated protein (MRP) isoforms and the breast cancer resistance protein (BCRP) mediate sulfate conjugate efflux out of BeWo cells
Article
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URL
https://kuscholarworks.ku.edu/bitstream/1808/7614/1/Audus_AFD_MRPandBCRP.pdf
File
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https://kuscholarworks.ku.edu/bitstream/1808/7614/3/Audus_AFD_MRPandBCRP.pdf.txt
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oai:kuscholarworks.ku.edu:1808/60252020-07-27T15:09:33Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Markham, Aaron P.
cmtemember
Siahaan, Teruna J.
cmtemember
Berkland, Cory J.
cmtemember
Krise, Jeffrey P.
cmtemember
Hefty, P Scott
2010-03-18T19:45:20Z
2010-03-18T19:45:20Z
2009-07-06
http://dissertations.umi.com/ku:10467
http://hdl.handle.net/1808/6025
Many gram-negative bacterial pathogens employ type III secretion systems (TTSS) to transport effector proteins into eukaryotic host cell membranes and cytoplasms to subvert normal cellular functions. TTSSs contain a basal body which spans the inner and outer bacterial membranes and a needle which extends the into extracellular space. With the increasing prevalence of drug resistant bacterial strains, vaccines represent one of the most promising strategies to combat these diseases. Proteins located at the extracellular needle tip of TTSSs appear to be excellent candidates for a sub-unit vaccine approach. These so called tip proteins are surface exposed and regulate the secretion of other effector proteins. This work presents pre-formulation, formulation and animal studies focused on creating a single multivalent sub-unit vaccine for five gram-negative pathogenic systems. In addition, a putative tip protein from Chlamydiae is compared to the other tip proteins using biophysical methods.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Antigen
Formulation
Subunit
Vaccine
CREATING A MULTIVALENT SUBUNIT VACCINE USING TYPE III SECRETION SYSTEM TIP PROTEINS AS ANTIGENS
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6025/1/Markham_ku_0099D_10467_DATA_1.pdf
File
MD5
1fdde4675779110779ec7a2e89693baa
1163956
application/pdf
Markham_ku_0099D_10467_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6025/2/Markham_ku_0099D_10467_DATA_1.pdf.txt
File
MD5
a3f8d9ba62ed0bf1d446f48c6270f771
269029
text/plain
Markham_ku_0099D_10467_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216702018-01-31T20:07:51Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stella, Valentino J
advisor
Jumaa, Mouhannad
author
Phizackerley, Kirsten (Kaci)
cmtemember
Stobaugh, John
2016-10-11T19:34:38Z
2016-10-11T19:34:38Z
2015-05-31
http://dissertations.umi.com/ku:13861
http://hdl.handle.net/1808/21670
Proteasome inhibitors are clinically effective treatment of multiple myeloma and mantle cell lymphoma. One proteasome inhibitor already on the market and one under clinical investigation are epoxy-ketones that potently and irreversibly bind to the proteasome. Kinetics were studied by loss of an fÑ-keto-epoxide, PR-020 Pivoyl (PIV-PR-020), a model for the warhead of a number of proteasome inhibitor anticancer agents, namely, carfilzomib and oprozomib, in aqueous solutions as a function of pH, temperature and solvent composition. The loss of PIV-PR-020 followed pseudo first order kinetics and provided a U-shaped pH-rate profile with an apparent pH-independent region between pH values of approximately 4 to 7. The degradation of PIV-PR-020 in aqueous solution was found to be both acid catalyzed below pH 4 and base catalyzed above pH 7. During the course of the study, the temperature, ionic strength, buffer concentration, and halide effect were evaluated while keeping the concentration of the reactant constant. Under acidic conditions, as you increase the halide nucleophilicity, the reactivity increases. The fÑ-keto-epoxide ring opening in an SN2 reaction under acidic conditions and is undefined under basic conditions. It has also been shown that there is some scrambling at the carbon at the C1 position at higher pH values due to base catalyzed isomerization, and there is evidence that this diastereomer further degrades to a diol. At pH 8, the rate equations are complex due to reversible and parallel reactions. The study of PIV-PR-020 provides insight into the likely routes and rates of degradation at the warhead of carfilzomib and oprozomib.
en
Copyright held by the author.
Pharmaceutical sciences
Chemistry
degradation
keto-epoxide
kinetics
proteasome inhibitor
Mechanism of Degradation of an alpha- Keto-Epoxide, PIV-PR-020: A Model for the Warhead for Various Proteasome Inhibitor Anticancer Agents
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21670/1/Phizackerley_ku_0099M_13861_DATA_1.pdf
File
MD5
f75c1cf9f23569f6769edd9ec083b28b
1000399
application/pdf
Phizackerley_ku_0099M_13861_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21670/2/Phizackerley_ku_0099M_13861_DATA_1.pdf.txt
File
MD5
deecb9a8e94684c44cb3a3e8c1bd9e56
54173
text/plain
Phizackerley_ku_0099M_13861_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/70092020-08-06T13:13:31Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Stobaugh, John F.
author
van Haandel, Leon
cmtemember
Schöneich, Christian
cmtemember
Lunte, Susan M.
cmtemember
Williams, Todd D.
cmtemember
Prisinzano, Thomas E.
2011-01-03T04:16:57Z
2011-01-03T04:16:57Z
2010-11-29
http://dissertations.umi.com/ku:11198
http://hdl.handle.net/1808/7009
This dissertation describes the development of bioanalytical strategies for a group of experimental and known therapeutic agents and chemically related essential substances. The array of analytes include the antifolate methotrexate, its various (in)active metabolites and related bio-conjugates, plus several forms of folic acid family, a group of essential substances not synthesized by mammalian species, but endogenously required in numerous biochemical processes. These analytes all share a common structural feature, the heterocyclic pteridine ring system. Analyte identity results from variations of the ptereridine-ring system redox state, a result of minor structural variations of the heterocyclic ring and changes in conjugation status (i.e. polyglutamated or nanoparticle conjugated). Specific and sensitive detection of the individual species was of high interest, as the various chemical forms of these substances may constitute biomarkers for individualizing low dose MTX therapy in autoimmune diseases such as JIA, but is also required for the (pre)clinical studies of novel nano-device MTX drug delivery systems. The dissertation presents state-of-the-art bioanalytical methodology suitable for the specific determination of any specific analyte in the presence of all other analytes. The strategy for each particular analyte possesses its own unique strength and weakness, with the final strategy collectively being based on the specific structure and associated physical-chemical property of a given analyte, the biological environment, and the clinical question to be answered.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Biochemistry
Autoimmune disease
Folate
Juvenile idiopathic arthritis
Methotrexate
Pamam dendrimer
Polyglutamation
Bioanalysis of Pteroyl Derivatives in Various Aspects of Human Health
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/7009/1/vanHaandel_ku_0099D_11198_DATA_1.pdf
File
MD5
cb67736a484f6915873fc19f6f2c965c
6623583
application/pdf
vanHaandel_ku_0099D_11198_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/7009/2/vanHaandel_ku_0099D_11198_DATA_1.pdf.txt
File
MD5
7f7f2168427fede784cea4fe73f8cff2
394131
text/plain
vanHaandel_ku_0099D_11198_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/253872021-03-05T19:15:26Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Tolbert, Thomas J.
author
Okbazghi, Solomon Zeray
cmtemember
Volkin, David B
cmtemember
Siahaan, Teruna J
cmtemember
Wang, Michael Z
cmtemember
Ray, Christian J
2017-11-16T04:09:15Z
2017-11-16T04:09:15Z
2017-08-31
http://dissertations.umi.com/ku:15439
http://hdl.handle.net/1808/25387
The patents of several best-selling biologic therapeutic products are expiring soon. Consequently, the interest of developing biosimilar products is growing. A biosimilar product is developed if there are no clinically meaningful differences in terms of safety, efficacy, and purity after evaluating side-by-side with the originator. Biosimilar products are anticipated to be accessible to healthcare providers and patients at a lower cost compared to the originators. Unlike small-molecule generic drug products, which are structurally replicable and well-defined, that guarantee the safety and efficacy, biologic products are structurally complex, larger in size and often contain mixtures of various posttranslational modifications. Consequently, demonstrating the similarity of a biosimilar molecule with the reference product requires extensive characterization to ensure safety and efficay. One of the challenges in developing a biosimilar product is the lack of knowledge about the reference product’s manufacturing process, which is not accessible to the public because it is a proprietary knowledge. Therefore, the biosimilar sponsor needs to develop a process by extensive characterization of a biosimilar candidate side-by-side with a reference product. This is an iterative process aimed at developing a biosimilar molecule similar to the reference product. The first step in biosimilarity assessment is to establish structural similarity by extensive characterization using several analytical techniques. Therefore, analytical tools play a vital role in demonstrating structural similarity as well as process development of a biosimilar candidate. In addition, the level of similarity established by the analytical tools guides the type of non-clinical and clinical data packages required for regulatory approval. If a high degree of similarity is demonstrated using analytical techniques, then phase II clinical trials are not required for registration of a biosimilar candidate. Consequently, this will lower the cost of developing a biosimilar product. Hence, developing sensitive and robust analytical techniques is vital in a biosimilar development process. In this dissertation, four homogeneous glycoforms of IgG1 Fc (HM-Fc, GlcNAc-Fc, Man5-Fc, and N297Q-Fc) were produced using recombinant protein expression combined with in-vitro enzymatic reactions to be utilized as a model for biosimilar comparability analysis. These glycoforms were characterized by mass spectrometry, CIUE, SDS-PAGE, and cIEF. The main focus of the project was to produce homogeneous glycoforms of IgG1 Fc and to utilize them to develop new biolayer interferometry (BLItz) assay methods. Two biolayer interferometry methods with different immobilization techniques were developed to measure the binding affinity of IgG1 Fc glycoforms to FcRIIIa and FcRIIb. In addition, these four glycoforms were mixed in pre-defined composition to examine the characteristics of mixtures of glycoforms and to study important biological and physicochemical features of protein drugs in a biosimilar analysis. For the mixture samples, differences in binding were observed when the two immobilization formats were employed. Furthermore, these glycoforms were incubated at low and elevated temperatures for an elongated time, and a trend of decreasing binding affinity was observed with the increasing incubation period.
en
Copyright held by the author.
Pharmaceutical sciences
Biosimilar
Comparability analysis
Functional activity
Glycoforms
IgG1 Fc
IgG antibody
Comparative Evaluation of Well-Defined IgG1 Fc Glycoforms as a Model System for Biosimilar Comparability Analysis
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25387/1/Okbazghi_ku_0099D_15439_DATA_1.pdf
File
MD5
372f4164f6176230b20921c951a119cf
7692577
application/pdf
Okbazghi_ku_0099D_15439_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/25387/2/Okbazghi_ku_0099D_15439_DATA_1.pdf.txt
File
MD5
c5eb11ba3e8d0f7472d1f5b3c6340d7a
434768
text/plain
Okbazghi_ku_0099D_15439_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/61812020-07-27T15:07:50Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Lunte, Susan M
author
Nandi, Pradyot
cmtemember
Stobaugh, John F.
cmtemember
Krise, Jeffrey P.
cmtemember
Nordheden, Karen
cmtemember
Berkland, Cory J.
cmtemember
Lacher, Nathan
2010-05-03T00:57:21Z
2010-05-03T00:57:21Z
2009-08-31
http://dissertations.umi.com/ku:10553
http://hdl.handle.net/1808/6181
Microdialysis is a sampling technique that can be employed to monitor biological events in vivo and chemical reactions in vitro. When it is coupled to an analytical system, microdialysis can provide near real time information on the time dependent concentration changes of analytes in the extracellular space or other aqueous environments. Online systems for the analysis of microdialysis samples enable fast, selective and sensitive analysis while preserving the temporal information. Analytical methods employed for on-line analysis include liquid chromatography (LC), capillary (CE) and microchip electrophoresis and flow-through biosensor devices. This dissertation is focused on the development of microchip systems coupled to microdialysis sampling for online near-real time monitoring with high temporal resolution for the analysis of amino acid neurotransmitters in vivo. Fluorescence detection was utilized for all the studies. Also, naphthalene-2,3-dicarboxaldehyde (NDA) and b-mercaptoethanol (b-ME) or CN- are used as the derivatization reagents for rendering the amino acids fluorescent. Initial studies were performed to evaluate a twin-t design with a 3 cm separation channel that incorporated on-column derivatization with NDA and b-ME. Biogenic amines and peptides were separated on chip demonstrating the feasibility of online microdialysis sampling with online derivatization and analysis in vitro. Subsequently, the chip was further modified by incorporating a 20 cm serpentine separation channel and excitatory amino acid neurotransmitters (glutamate, aspartate) were separated from other analytes in rat brain microdialysis samples. Next, precolumn derivatization was incorporated into the chip and online in vivo experiments were performed for the continuous analysis of glutamate from rat brain microdialysis sample. Also, fluorescein was included in the experiment for the possibility to simultaneously monitor the permeability of the blood brain barrier (BBB) along with changes in levels of excitatory neurotransmitters during online analysis applied to the rat stroke model. The chip was further modified and optimized for experiments that require fast injections and separations thereby attaining high temporal resolution. This work described an online microdialysis-microchip system that can be used for monitoring neurochemical events that involve fast changes in analyte concentration in the brain.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Analytical chemistry
Pharmaceutical chemistry
Brain microdialysis
Microchip electrophoresis
Nda
Online derivatization
Serpentine microchips
Development of online microdialysis-microchip system for in vivo monitoring
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6181/1/Nandi_ku_0099D_10553_DATA_1.pdf
File
MD5
b7b376b4608de58de5edfa361ddb1711
2561529
application/pdf
Nandi_ku_0099D_10553_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6181/2/Nandi_ku_0099D_10553_DATA_1.pdf.txt
File
MD5
fc41ebd58dca799a7bb9daf5b6ebeb88
229296
text/plain
Nandi_ku_0099D_10553_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216352020-10-22T13:31:11Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John F
author
Morgan, Carrie Marie
cmtemember
Siahaan, Teruna J
cmtemember
Forrest, Laird
2016-10-11T16:07:21Z
2016-10-11T16:07:21Z
2014-05-31
http://dissertations.umi.com/ku:13216
http://hdl.handle.net/1808/21635
Abstract Improving the solubility and changing the dissolution rate of the poorly soluble active pharmaceutical ingredients (API's) AMG 517, glipizide, and naproxen through the preparation of eutectic mixtures was investigated. Mixtures of the API's with other small molecules were prepared to construct a phase diagram used to identify the eutectic mixture compositions. The search for a eutectic mixture in a co-crystal phase diagram was investigated by mixing AMG 517 with known co-crystal formers sorbic acid and trans–cinnamic acid. Glipizide was mixed with a series of amides to investigate the presence of eutectic mixtures, but the thermal instability of the API was such that chemical degradation overwhelmed any other thermal transitions. A phase diagram of naproxen and vanillin was prepared and the composition of the eutectic mixture identified. The eutectic mixture at 0.11 MF naproxen vanillin (11% naproxen/ 89% vanillin) was found to have a melting point of 75 °C. The melt is reversible and thermally stable, as tested by multiple melts and coolings. Further studies are planned to evaluate whether the eutectic mixture may be advantageous to develop. However, expectations are modest due to the small amount of naproxen present in the eutectic mixture.
en
Copyright held by the author.
Pharmaceutical sciences
AMG 517
Eutectic Mixtures
glipizide
naproxen
Investigating Eutectic Mixtures for Poorly Soluble Compounds
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21635/1/Morgan_ku_0099M_13216_DATA_1.pdf
File
MD5
97bcdc3b01286cc67f7670effb2d1417
7032472
application/pdf
Morgan_ku_0099M_13216_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21635/2/Morgan_ku_0099M_13216_DATA_1.pdf.txt
File
MD5
66c6771e76bf1e21f14111d635f65a5d
174847
text/plain
Morgan_ku_0099M_13216_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216592018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Middaugh, Charles R
author
Alabdulkarim, Abdullah
cmtemember
Volkin, David B
cmtemember
Berkland, Cory J
2016-10-11T19:08:36Z
2016-10-11T19:08:36Z
2015-05-31
http://dissertations.umi.com/ku:14446
http://hdl.handle.net/1808/21659
The World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) estimate globally that 1.9 million children under the age of five years old die annually as consequence of diarrhea. Increasing need for hospitalization, which has negative effects on health care sectors, in addition to mortality incidences mark diarrheal related diseases a growing burden on both health care sectors and the global economy. Introducing novel measures to control and avert the spread of diarrheal disease are of paramount importance. Diarrhea is the main symptom in Acute gastroenteritis (AGE) and according to the United States' National Outbreak Reporting System (NORS), viral agents are the dominant precursors of epidemic AGE outbreaks. More than 90% of humans' acute non-bacterial gastroenteritis breakouts worldwide is caused by Noroviruses (NoVs). NoVs of the Caliciviridae family are none enveloped, positive sense, single stranded RNA virus, noncultivable in cell culture, containing three open reading frames (ORF). Expressing NoVs ORF2 in a baculovirus expression system produces empty virus-like particles (VLPs). These VLPs are very similar to the native virus in terms of morphology and antigenicity, yet lacking the genetic material essential for infectivity, making the VLPs a superb candidate for vaccine development. By comparing the capsid sequence of three different NoVs GII.4 strains, consensus GII.4 VLPs were produced as a potential vaccine with the goal of providing a broader protection against AGE. The main objective of this study is to understand the structural behavior of NoVs Consensus GII.4 VLPs, which is to be used as a vaccine. A complement of biophysical techniques has been employed to characterize the physical stability of Noroviruses Consensus GII.4 virus-like particles (VLPs) as a function of temperature and pH. The VLPs' physical stability are characterized by different spectroscopic techniques and the resulting data are used to construct empirical phase diagrams (EPDs) projecting the entire data set in the form of a colored image. These EPDs are used in the development of excipient screening assays to identify potential stabilizers of the VLPs in solution. The identified stabilizers are then subjected to further screening using fluorescence analysis to determine their optimal concentrations and use in combination. The generated data are used to construct binding isotherms for Consensus GII.4 VLP and aluminum salt adjuvants (Alhydrogel® and Adjuphos®). Binding isotherms were also generated for Norwalk VLP (a previously studied vaccine candidate) and aluminum salt adjuvants. Front Face Fluorescence Spectroscopy is used to evaluate the structural changes associated with Consensus GII.4 and Norwalk VLPs when bound to aluminum salt adjuvants.
en
Copyright held by the author.
Pharmaceutical sciences
CONSENSUS GII.4 VIRUS LIKE PARTICLES; A VACCINE CANDIDATE BIOPHYSICAL CHARACTERIZATION, STABILIZATION, AND ADJUVANTS BINDING STUDIES
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21659/1/Alabdulkarim_ku_0099M_14446_DATA_1.pdf
File
MD5
25e5537d3ace81d53361843cdc6666fc
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Alabdulkarim_ku_0099M_14446_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21659/2/Alabdulkarim_ku_0099M_14446_DATA_1.pdf.txt
File
MD5
3a40a71367f8a5b23faf62beb7297bce
75085
text/plain
Alabdulkarim_ku_0099M_14446_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/267502018-09-27T08:01:19Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
author
Shull, Charles Scott
2018-09-26T15:27:56Z
2018-09-26T15:27:56Z
1951
http://hdl.handle.net/1808/26750
This work is in the public domain and is available for users to copy, use, and redistribute in part or in whole. No known restrictions apply to the work.
Synthesis of amebacidal acridines
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/26750/1/shull_1951_3430365.pdf
File
MD5
be9ac333741673a07a607ad804dbce24
27302824
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shull_1951_3430365.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/26750/2/shull_1951_3430365.pdf.txt
File
MD5
375c7093211b973e759a3cab249be2d0
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shull_1951_3430365.pdf.txt
oai:kuscholarworks.ku.edu:1808/61862018-11-27T19:13:41Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Barrett, Brooke S.
cmtemember
Lunte, Susan M.
cmtemember
Siahaan, Teruna J.
cmtemember
Berkland, Cory J.
cmtemember
Picking, William
2010-05-03T01:15:20Z
2010-05-03T01:15:20Z
2009-04-02
http://dissertations.umi.com/ku:10227
http://hdl.handle.net/1808/6186
Recombinant protein vaccines are fast becoming the focus of the vaccine industry due to their increased safety. Here we examine the development of several recombinant protein vaccines and the challenges involved. Once an antigen is identified, and a process to recombinantly produce the protein established, the first step is to perform a biophysical characterization of the macromolecule. The protein is stressed with respect to variables such as temperature and pH and monitored for perturbations in physical structure indicating potential sources of instability. In the second step, we examine aspects of formulation such as excipient screening and adjuvant adsorption which may enhance the antigen immunogenicity and stability. The third step involves evaluating the working formulation in an animal model to establish dose dependency and the effect of the adjuvant. Finally, accelerated and real-time stability studies are being completed, and the formulations adjusted accordingly.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Physical chemistry
Recombinant protein vaccines
Ricin toxin
Salmonella typhimurium
Shigella flexneri
Spectroscopic biophysical characterization
Type three secretion system
Formulation and Development of Recombinant Protein Vaccines
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6186/1/Barrett_ku_0099D_10227_DATA_1.pdf
File
MD5
b56e572187689e03626aace8e0d04ebb
5271678
application/pdf
Barrett_ku_0099D_10227_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6186/2/Barrett_ku_0099D_10227_DATA_1.pdf.txt
File
MD5
d5c787429aa10471116f6acea84b7ebd
233733
text/plain
Barrett_ku_0099D_10227_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216602018-01-31T20:07:52Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Volkin, David
author
Woods, Christopher E.
cmtemember
He, Feng
cmtemember
Tolbert, Thomas
2016-10-11T19:10:54Z
2016-10-11T19:10:54Z
2015-12-31
http://dissertations.umi.com/ku:14272
http://hdl.handle.net/1808/21660
Aggregation has been identified as one of the major degradation pathways that affect the quality and efficacy of protein therapeutics. Dimers are one of the predominant oligomeric species found in monoclonal antibody (mAb) based products, whose formation can occur both during processing and long-term storage, and following exposure to certain accelerated stress conditions. It has been hypothesized that these dimeric species could be the initial step on the mAb protein aggregation pathway, but this has been difficult to establish since mAb dimers can be a heterogeneous population of molecules. In this study, two mAb dimer species were generated and isolated from IgG2 monoclonal antibody samples, one upon long-term storage and the other from elevated stress conditions. The dimer-enriched fractions were characterized for protein conformation, morphology, structural integrity and bioactivity. The results revealed both common properties and unique differences between the two types of mAb dimers generated under these two different conditions. The findings of this study provide insights towards greater understanding of the possible causes of dimer formation under native storage and thermal stress conditions for this IgG2 mAb, and two possible mechanisms of dimer formation are proposed.
en
Copyright held by the author.
Pharmaceutical sciences
Pharmacology
Biochemistry
Biophysical Analysis
Hydrogen-Deuterium Exchange
Immunoglobulin G
Monoclonal Antibody
Protein Aggregation
Understanding Therapeutic Monoclonal Antibody Aggregation Mechanisms through Biophysical, Biochemical and Biological Characterization of Two Types of Immunoglobulin G Dimers
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21660/1/Woods_ku_0099M_14272_DATA_1.pdf
File
MD5
b2024dfc7721db5fb1ed6dcc5d8d3bb8
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Woods_ku_0099M_14272_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21660/2/Woods_ku_0099M_14272_DATA_1.pdf.txt
File
MD5
05dbaef0698f473319140f7bcb1da8ae
124072
text/plain
Woods_ku_0099M_14272_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/302152021-03-05T19:03:59Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Berkland, Cory J
author
Mihalcin, Melissa Marie
cmtemember
Forrest, Laird
cmtemember
Stobaugh, John
cmtemember
Krise, Jeff
cmtemember
Dhar, Prajnaparamita
2020-03-29T16:45:05Z
2020-03-29T16:45:05Z
2019-12-31
http://dissertations.umi.com/ku:16908
http://hdl.handle.net/1808/30215
https://orcid.org/0000-0001-9255-0699
Cancer immunotherapy involves stimulation of the body’s own immune system to fight cancer. Tumors possess myriad suppressive mechanisms that facilitate evasion of the immune system. Immunotherapy aims to stimulate immune cells to recognize and attack tumor tissue. While immunostimulatory agents have achieved some success in treating cancer, systemic toxicity remains a major concern. In particular, systemic exposure to immunostimulants can activate immune cells outside of target tissues, which can potentially induce side effects or autoimmune reactions. In the treatment of solid tumors, intratumoral (IT) therapy offers unique benefits as an anti-cancer strategy, especially in the ability to bypass obstacles of trafficking, tumor penetration, and severe adverse events associated with systemic delivery. IT administration of immunostimulants, for example, can work synergistically with checkpoint inhibitors making a nonresponsive ‘cold’ tumor ‘hot’ by recruiting and activating tumor infiltrating lymphocytes. Unfortunately IT administration does not necessarily preclude the manifestation of systemic adverse events; therapy transport out of the tumor and back into systemic circulation can lead to similar adverse events as seen with systemic exposure. While many researchers have worked to optimize the efficacy of immunostimulants, few have approached delivery design with the consideration of drug retention after IT administration. This dissertation sought to explore delivery strategies for two negatively charged immunostimulants, polyI:C and CpG, which are potent toll-like receptor 3 (TLR3) and TLR9 agonists, respectively. Both compounds exhibit strong induction of interferons, leading to a proinflammatory environment after binding to TLRs, thus generating memory and tumor-specific T cells. Both TLR3 and TLR9 are located intracellularly; thus negatively-charged polyI:C and CpG macromolecules must be internalized by immune cells in order to be efficacious. To achieve both goals of increased retention and intracellular delivery, polycations were selected as a delivery tool. Polycations have historically been employed for intracellular delivery of nucleic acid material. This dissertation suggests that electrostatics can aid in injection site retention through interactions with highly negatively charged extracellular matrix. In chapter 2, polylysine, at a range of molecular weights, was evaluated for its ability to complex with immunostimulants and subsequently activate TLR(s). Chapter 3 presented a novel idea utilizing Glatiramer Acetate (GA), better known as Copaxone® as a delivery tool for immunostimulants. GA is a highly positively-charged polypeptide and is currently an FDA-approved therapy for multiple sclerosis. In this work, we generated small nanoparticles known as polyplexes, which form when mixing positively-charged GA and negatively-charged immunostimulant(s) (polyI:C or CpG). Together from chapters 2 and 3, we found that the relationship between complexation and TLR activation depends on the strength of the interaction in the polyplex. In a tumor model of head and neck squamous cell carcinoma, GA polyplexes were able to decrease tumor burden as compared to the vehicle controls. Therefore, this dissertation demonstrates that using polycations to complex with immunostimulant(s) is a promising approach to effectively deliver therapies and stimulate a local immune response.
en
Copyright held by the author.
Pharmaceutical sciences
drug delivery
glatiramer acetate
immunostimulant
immunotherapy
polycation
toll-like receptor agonist
Design of Intratumoral Immunostimulant Formulations
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/30215/1/Mihalcin_ku_0099D_16908_DATA_1.pdf
File
MD5
4d1fedf7bce3de46e5cdb171f2cd745f
6859975
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Mihalcin_ku_0099D_16908_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/30215/2/Mihalcin_ku_0099D_16908_DATA_1.pdf.txt
File
MD5
ee4147212899a4c7fe348a220a0057f9
333317
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Mihalcin_ku_0099D_16908_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/70112018-01-31T20:08:09Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John F.
author
MacLean, Jenifer Anne
cmtemember
Nagapudi, Karthik
cmtemember
Munson, Eric J.
2011-01-03T04:20:00Z
2011-01-03T04:20:00Z
2010-12-16
http://dissertations.umi.com/ku:11252
http://hdl.handle.net/1808/7011
ABSTRACT In this paper we explore the use of Neusilin, an inorganic magnesium aluminometasilicate, to stabilize the amorphous form of an acidic drug a neutral drug and two basic drugs. Both cryomilling and ball milling of the drug with Neusilin were found to produce the amorphous phase. However the ball milled material exhibited superior physical stability when compared to the cryomilled material at 40 oC/75% RH. 13C SSNMR investigation of the ball milled material revealed an acid-base reaction between the acidic drug and Neusilin. Optimal milling conditions and the kinetics of salt formation were also established. As bench-top milling is a lab scale process, a scalable process was developed to make the acidic drug/Neusilin amorphous drug complex using Hot Melt Extrusion (HME). The dissolution properties of the resulting HME material was found to have been improved over the material made by bench top milling while maintaining similar physical stability. The HME material was used to make tablets using a direct compression method. The HME tablets were found to outperform tablets made from crystalline Sulindac. For the broad class of acidic drugs containing the carboxyl moiety, Neusilin or other similar silicates would be better choices to stabilize amorphous phase than organic polymers.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Amorphous
Pharmaceutics
Stabilization
FORMATION OF A PHYSICALLY STABLE AMORPHOUS DRUG COMPLEX
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/7011/1/MacLean_ku_0099M_11252_DATA_1.pdf
File
MD5
f000f8129d5bede67540797c54e5337b
1575808
application/pdf
MacLean_ku_0099M_11252_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/7011/2/MacLean_ku_0099M_11252_DATA_1.pdf.txt
File
MD5
10d0b58d2f3dc4c51585d16f44bd9286
139307
text/plain
MacLean_ku_0099M_11252_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/278342020-07-09T21:33:16Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Schöneich, Christian
author
Bommana, Rupesh
cmtemember
Volkin, David B
cmtemember
Wang, Zhou (Michael)
cmtemember
Tolbert, Thomas J
cmtemember
Deeds, Eric
2019-05-10T16:12:24Z
2019-05-10T16:12:24Z
2017-12-31
http://dissertations.umi.com/ku:15617
http://hdl.handle.net/1808/27834
Protein-based pharmaceuticals are a fast growing class of therapeutics, which are widely used in the treatment of various diseases such as cancers and autoimmune diseases. Proteins are susceptible to multiple degradation pathways including oxidation, deamidation and photodegradation. Over the past decade, the pharmaceutical industry has become increasingly cognizant of the sensitivity of proteins towards light. The exposure of proteins to light during their development and patient administration is inevitable, and may result in protein degradation. In the recent past there have been multiple reports indicating formation of aggregates, discoloration, oxidation, covalent crosslinking and fragmentation on exposure of protein pharmaceuticals to light. These degradation pathways could enhance immunogenicity or cause inactivation. Therefore, to increase the stability of these proteins, an understanding of their degradation is necessary. The research covered in this dissertation focused on two major degradation mechanisms for an IgG monoclonal antibody (mAb): chemical and physical degradation by photo irradiation. First, this dissertation explored the effects of certain pharmaceutical excipients on the extent and site-specificity of epimerization in UV irradiated mAb formulations. Amino acid analysis of UV irradiated mAb revealed formation of D-Ala, D-Glu, and D-Val in mAb formulations. Secondly, the underlying mechanism behind the increased aggregation propensity of a photo irradiated IgG1 mAb was investigated using hydrogen deuterium exchange mass spectrometry and biophysical characterization. Specific correlations were established between changes in dynamics of distinct segments in the CH2 domain of the IgG1 mAb and decreased thermal stability as well as increase in aggregation propensity of the IgG1 mAb on light exposure. This dissertation also describes development of a rapid screening methodology to identify protein oxidation by monitoring Tyr and Phe oxidation using fluorogenic derivatization. The Fluorogenic derivatization technique was adapted to a 96-well plate, in which several protein formulations can be screened in a short time. In addition, this dissertation also outlines the capability of an extreme ultra pressure liquid chromatography system in investigating complex chemical degradation problems.
en
Copyright held by the author.
Pharmaceutical sciences
Chemistry
Biochemistry
amino acid analysis
fluorogenic derivatization
hydrogen deuterium exchange mass spectrometry
light exposure
monoclonal antibody
protein degradation
Degradation of therapeutic proteins: Screening methods and identification of epimerized amino acids and local conformational changes in light exposed proteins
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/27834/1/Bommana_ku_0099D_15617_DATA_1.pdf
File
MD5
a224c722eb66a60dda0cdffe2cbf612d
8727633
application/pdf
Bommana_ku_0099D_15617_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/27834/2/Bommana_ku_0099D_15617_DATA_1.pdf.txt
File
MD5
f320eed54ac606578789c4d7139f6559
295712
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Bommana_ku_0099D_15617_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216542018-11-01T18:10:53Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Schöneich, Christian
author
Yang, Yi
cmtemember
Stobaugh, John F.
cmtemember
Gennaro, Lynn
2016-10-11T18:56:12Z
2016-10-11T18:56:12Z
2016-05-31
http://dissertations.umi.com/ku:14473
http://hdl.handle.net/1808/21654
https://orcid.org/0000-0002-7869-2858
In the biotechnology industry, oxidative carbonylation as a post-translational modification of protein pharmaceuticals has not been studied in detail. Using Quality by Design (QbD) principles, understanding the impact of oxidative carbonylation on product quality of protein pharmaceuticals, particularly from a site-specific perspective, is critical. However, comprehensive identification of carbonylation sites has so far remained a very difficult analytical challenge for the industry. In this work, for the first time the identification of specific carbonylation sites on recombinant monoclonal antibodies was reported using a new analytical approach via derivatization with Girard's Reagent T (GRT) and subsequent peptide mapping with high-resolution mass spectrometry. Enhanced ionization efficiency and high quality MS2 data resulted from GRT derivatization were observed as key benefits of this approach, which enabled direct identification of carbonylation sites without any fractionation or affinity enrichment steps. A simple data filtering process was also incorporated to significantly reduce false positive assignments. Sensitivity and efficiency of this approach were demonstrated by identification of carbonylation sites on both unstressed and oxidized antibody bulk drug substances. The applicability of this approach was further demonstrated by identification of 14 common carbonylation sites on three highly similar IgG1s. This approach represents a significant improvement to the existing analytical methodologies and facilitates extended characterization of oxidative carbonylation on recombinant monoclonal antibodies and potentially other protein pharmaceuticals in the biotechnology industry.
en
Copyright held by the author.
Pharmaceutical sciences
critical quality attributes
metal catalyzed oxidation
oxidative carbonylation
post-translational modification
recombinant monoclonal antibody
Site-Specific Characterization of Oxidative Carbonylation on Recombinant Monoclonal Antibodies
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/21654/1/Yang_ku_0099M_14473_DATA_1.pdf
File
MD5
a6a4aa269f7814f1d69edd0fb8b2ceac
1252588
application/pdf
Yang_ku_0099M_14473_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/21654/2/Yang_ku_0099M_14473_DATA_1.pdf.txt
File
MD5
a96c73508bc0c00bec7f0ae7a66f11df
77447
text/plain
Yang_ku_0099M_14473_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/62992020-07-30T14:49:17Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Middaugh, C. Russell
author
Kissmann, Julian Michael
cmtemember
Siahaan, Teruna J.
cmtemember
David, Sunil A.
cmtemember
Laurence, Jennifer S.
cmtemember
Forrest, Laird
2010-06-09T04:02:32Z
2010-06-09T04:02:32Z
2010-04-20
http://dissertations.umi.com/ku:10875
http://hdl.handle.net/1808/6299
This dissertation describes the application of a composite biophysical approach to the characterization and stabilization of viruses and virus-like particles for vaccine purposes. Spectroscopic, calorimetric, and light-scattering techniques were applied to detect physical changes in multiple aspects of viral architecture following the application of pharmaceutically relevant stress factors. The signals from a variety of these techniques were then combined in a vector-based approach to generate empirical phase diagrams that visually depict changes in each system's physical state as a function of experimental stress factors. These diagrams were then used to determine optimal solution storage conditions and also conditions for screening excipient libraries for appropriate stabilizers.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Formulation
Influenza
Measles
Stabilization
Vaccine
Virus-like particles
The Application of Empirical Phase Diagrams to the Biophysical Characterization and Stabilization of Viral Vaccine Candidates
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/6299/1/Kissmann_ku_0099D_10875_DATA_1.pdf
File
MD5
c7dcbcf6301b4dc82fdf777cb74d0301
3168296
application/pdf
Kissmann_ku_0099D_10875_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/6299/2/Kissmann_ku_0099D_10875_DATA_1.pdf.txt
File
MD5
11d6bccf1f2353ca0c2d3cf394f0b2a1
222980
text/plain
Kissmann_ku_0099D_10875_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/106212020-09-22T13:39:56Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Stobaugh, John F.
author
Miller, Elise
cmtemember
Forrest, Laird
cmtemember
Wuelfing, W. P
2013-01-20T15:01:24Z
2013-01-20T15:01:24Z
2012-12-31
http://dissertations.umi.com/ku:12515
http://hdl.handle.net/1808/10621
https://orcid.org/0000-0003-4788-9874
Studied for decades, ionic liquids have largely been used as solvents in the pharmaceutical industry. An active ionic liquid (AIL) contains an active pharmaceutical ingredient (API) as one of the counterions. They have to potential to be advantageous in traditional oral and alternative non-oral routes of administration. The library of successful AILs was increased with a series of generic and propriatary compounds. They were characterized via infrared spectrometry, glass transition temperature, residual solvent, salt factor and biorelevant solubility. The impact of counterion selection on physical properties was discussed for three series of AILs. Issues with purification and the impact of residual solvent were investigated. While the equilibrium solubility enhancement of AILs over their neutral forms was not as high as hoped for, the dissolution rate advantage and utility for liquid dosing remains to be investigated.
en
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical sciences
Investigations into the Synthesis, Identification and Developability of Active Ionic Liquids
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/10621/1/Miller_ku_0099M_12515_DATA_1.pdf
File
MD5
5c8bd94830b46d5b43a1bb9a20bbbb96
2687769
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Miller_ku_0099M_12515_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/10621/2/Miller_ku_0099M_12515_DATA_1.pdf.txt
File
MD5
ece9b3a853d3bea82b2249cad295866a
83515
text/plain
Miller_ku_0099M_12515_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/273382019-01-17T17:34:07Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Lunte, Susan M
author
Al-Hossaini, Abdullah
cmtemember
Stobaugh, John F
cmtemember
Siahaan, Teruna J
cmtemember
Wang, Michael Z
cmtemember
Kuczera, Krzysztof
2018-11-13T23:48:53Z
2018-11-13T23:48:53Z
2017-12-31
http://dissertations.umi.com/ku:15573
http://hdl.handle.net/1808/27338
Dynorphin A 1-17 [Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln] is an endogenous opioid peptide. It is widely distributed in blood and CNS tissue and exhibits a high affinity to the kappa (κ) opioid receptors and binds with less affinity to both delta (δ) and mu (µ) opioid receptors. This peptide has been found to show both antinociceptive and analgesic effects within the central nervous system. Dyn A is also involved in the body’s immune response, in addition to control of heart rate, blood pressure, body temperature and feeding behavior. However, upregulation of Dyn A due to disease states has been shown to cause nonopioid activity such as hyperalgesia, allodynia, and excitotoxicity. In addition, altered levels of the neuropeptide have been linked to neurological disorders, including Alzheimer’s and Parkinson’s disease. Capillary electrophoresis is a powerful technique that can achieve high-efficiency separations of charged analytes. However, CE has limited use for the analysis of basic proteins and peptides, due to their adsorption onto the inner surface of the fused silica at pHs below their pI. This adsorption can lead to a loss of efficiency, irreproducibility of migration times, and peak tailing. This thesis describes the separation of dynorphin A 1-17 and its key metabolites using fused silica capillaries coated with positively charged polydiallyldimethylammonium chloride (pDDA) and pDDA stabilized gold nanoparticles modified capillaries. The coating material minimized unwanted adsorption of the positively charged peptides onto the surface of the fused-silica capillary. The studies with capillary electrophoresis were performed using UV detection at 214 nm. However, the detection limits are too high to determine endogenous concentrations of these bioactive peptides in brain microdialysis samples. To improve the detection limits, while still maintaining small sample volume requirements, the development of glass and glass/polydimethylsiloxane microchip electrophoresis (ME) system with fluorescence detection is described. Several fluorescence tags were evaluated including the fluorescent probe, fluorescein isothiocyanate, and the fluorogenic probe, naphthalene-2,3-dicarboxaldehyde with sodium cyanide, which produces a fluorescent 1-cyanobenz[f]isoindole (CBI) derivative. The ME-LIF system was shown to separate CBI-peptides of derivatized fragments of dynorphin A.
en
Copyright held by the author.
Pharmaceutical sciences
Capillary Electrophoresis
Dynorphin A
Gold nanoparticles
Microchip electrophoresis
Analytical Methods for the Study of Opioid Peptides
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/27338/1/ALHOSSAINI_ku_0099D_15573_DATA_1.pdf
File
MD5
b5cc0cb41fd76d4aed3c3eb92705de5f
3920378
application/pdf
ALHOSSAINI_ku_0099D_15573_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/27338/2/ALHOSSAINI_ku_0099D_15573_DATA_1.pdf.txt
File
MD5
b77b029c7a07675d809ce34643beceb2
280785
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ALHOSSAINI_ku_0099D_15573_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/302012021-03-05T16:54:48Zcom_1808_80com_1808_1260col_1808_14157col_1808_1951
KU ScholarWorks
advisor
Picking, William D
author
Skaar, Ryan Richard
cmtemember
Middaugh, Russ
cmtemember
Berkland, Cory J
2020-03-28T20:53:38Z
2020-03-28T20:53:38Z
2019-12-31
http://dissertations.umi.com/ku:16792
http://hdl.handle.net/1808/30201
https://orcid.org/0000-0001-5790-0032
Enteric infections, particularly those leading to diarrhea, can profoundly disrupt intestinal function and have a major impact on global mortality and morbidity rates.1 Globally, there are 1.7 billion cases of childhood diarrheal disease every year, which results in the death of approximately 525,000 children under the age of 5.2 Four pathogens were identified to be the key contributors to childhood diarrheal cases. These pathogens include rotavirus, Cryptosporidium, Shigella, and ST-ETEC. While rotavirus is the most prominent contributor to diarrheal episodes, specifically in infants (0 – 11 months), Shigella’s influence grows and becomes the primary contributor to diarrheal episodes as the child reaches the toddler stage of development (24 – 59 months).3 Ingestion of Shigella bacterium results in the luminal infection referred to as shigellosis. Before symptoms appear, Shigella first crosses the colonic epithelium via M cells where it is engulfed by macrophages that then undergo pyroptosis. After release into the sub-mucosa, Shigella invades intestinal epithelial cells using its type III secretion system (T3SS). The T3SS or injectisome is essential for Shigella virulence. The injectisome consists of three major components: extracellular needle, basal body, and a cytoplasmic sorting platform. Effector secretion is triggered by host cell contact and controlled by the sorting platform (SP). Shigella’s SP is comprised of five essential virulence proteins (MxiG, MxiK, Spa33, MxiN, and Spa47), which are highly conserved across all Shigella species. Characterization of the cytoplasmic SP via cryo-electron tomography allowed us to generate a 3D model of the SP containing six pod-like structures (comprised most prominently of Spa33). Spa33 is then connected to MxiN spokes that link it to the central ATPase (Spa47) and to MxiK, which links it to the basal body. This model differs dramatically from the contiguous arrangement of C ring proteins seen within the distantly related Gram-negative flagellum. Deletion of spa33 results in complete loss of the SP. Spa33 consists minimally of a dimer of C-terminal Spa33 domains (Spa33C) and a full-length copy (Spa33FL). Spa33FL is unstable on its own, but is greatly stabilized by association with its alternatively translated Spa33C dimer. Here I provide support using various biophysical techniques in vivo and in vitro that the association between Spa33FL and Spa33C is essential to T3SS function, suggesting that both Spa33FL and Spa33C are necessary for SP assembly in Shigella.
en
Copyright held by the author.
Molecular biology
characterization
Shigella
Sorting Platform
Spa33
T3SS
Type III Secretion System
Analysis of Spa33 and its Role in T3SS Cytoplasmic Sorting Platform of Shigella
Thesis
URL
https://kuscholarworks.ku.edu/bitstream/1808/30201/1/Skaar_ku_0099M_16792_DATA_1.pdf
File
MD5
2a0366b799048e289c077534fe54b90c
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Skaar_ku_0099M_16792_DATA_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/30201/2/Skaar_ku_0099M_16792_DATA_1.pdf.txt
File
MD5
f904fc12174695f8460fd7cd74fa06ff
128269
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Skaar_ku_0099M_16792_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/40992020-07-16T12:24:22Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Siahaan, Teruna J.
author
Trivedi, Maulik
2008-09-07T19:21:47Z
2008-09-07T19:21:47Z
2008-01-30
http://dissertations.umi.com/ku:2368
http://hdl.handle.net/1808/4099
The EC1 protein has an important role in the E-cadherin mediated cell-cell adhesion in epithelial and endothelial tissues. It may be used as modulator of cellular adhesion to improve paracellular delivery of macromolecules. EC1 undergoes oxidation of its Cys residue to form disulfide-linked covalent dimers. These dimers associate to form physical oligomers. The dimerization and oligomerization also lead to hydrolysis of the Asp93-Pro94 peptide bond and precipitation. To be able to study the cell adhesion-modulating activity of EC1, it is important that we block its disulfide-dimerization and subsequent oligomerization. The strategies used to block the dimerization were addition of dithiothreitol to the EC1 solution, modification of the Cys thiol with iodoacetamide and polyethylene glycol. These derivatives were studied for their stability using HPLC, CD and fluorescence spectroscopy. All strategies applied showed improvement in the stability of EC1. The PEGylated EC1 showed the best stability.
EN
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
Pharmaceutical chemistry
Improvement of the chemical and physical stability of the EC1 domain of E-cadherin by blocking its disulfide-mediated dimerization
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/4099/1/umi-ku-2368_1.pdf
File
MD5
512fd55bdc4c656bc29137cc7b76693c
1275142
application/pdf
umi-ku-2368_1.pdf
URL
https://kuscholarworks.ku.edu/bitstream/1808/4099/2/umi-ku-2368_1.pdf.txt
File
MD5
6db3e33df7358cab76e03a066193748a
214691
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umi-ku-2368_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/254302018-11-27T17:37:48Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Wang, Michael Z.
author
Chen, Yao
cmtemember
Stella, Valentino J.
cmtemember
Stobaugh, John F.
cmtemember
Berkland, Cory J.
cmtemember
Staudinger, Jeff L.
2017-11-17T22:21:36Z
2017-11-17T22:21:36Z
2016-12-31
http://dissertations.umi.com/ku:14950
http://hdl.handle.net/1808/25430
Quantification of highly homologous human liver drug-metabolizing enzymes (DMEs) has been a challenging task in drug metabolism and disposition research, due to a lack of specific antibodies and marker substrates. Mass spectrometry (MS) techniques and applications have evolved significantly, striving to achieve absolute and specific quantification of these enzymes. Since the first absolute quantification of cytochrome P450s (CYPs) using the attachment of isotope tags to free thiols (iCAT), MS-based quantification has become much more versatile, cheaper, and easier to use. Today, variations of liquid chromatography-multiple reaction monitoring (LC-MRM)-based targeted proteomics, such as AQUA (absolute quantification) and QconCAT (concatenated signature peptides), have become the gold standards for quantification. These new methods have driven the absolute quantification of DMEs to become a routine laboratory task. Many drug metabolism-related projects require absolute enzyme quantification. For example, precise knowledge of enzyme expression during ontogeny is a necessity to aid pharmacists in planning drug-dosing regimens for patients of different age groups. Additional examples include the need for accurate cellular enzyme expression profiles when establishing new drug-screening cell models and when elucidating molecular mechanisms underlying hypothesized drug-drug interactions. This dissertation demonstrates how an LC-MRM targeted approach contributes to these three areas. First, an ultra-performance liquid chromatography (UPLC)-MRM targeted quantification method was developed and validated, focusing specifically on the quantification of CYP2C and flavin-containing monoxoygenase (FMO) isoforms. Second, the newly developed, as well as existing, UPLC-MRM quantification methods were used to confirm previously reported DME ontogeny patterns and establish patterns for CYP4F and FMO5. Third, targeted proteomic quantification was employed for the absolute quantification of CYPs 1A1, 1A2 and 1B1 in KLE cells and different human tissue microsomes to aid the establishment of CYP1B1-dependent cell models for the screening of anticancer prodrugs. Lastly, CYP4F2-specific targeted quantification was used to confirm the mechanism underlying a potential drug-drug interaction between warfarin and lovastatin. UPLC-MRM-based targeted proteomic techniques have many advantages, but the cost and time required for method development rises linearly with an increase in the number of targeted proteins. An emerging technique utilizing label-free data independent analysis (DIA) with high-resolution mass spectrometry (HDMS) offers the global quantification of hundreds of proteins at a negligible cost; however, there are numerous hurdles when using this technique. We introduced a new sample processing method, quantitative filter-assisted sample preparation (qFASP), which allows full recovery and analysis of clean, digested proteomic peptides. With qFASP and additional optimized procedures, many of the hurdles encountered with DIA quantification were mitigated. Very strong quantitative correlations were observed between the new DIA/ HDMS technique and the well-established targeted proteomics for DME quantification. In summary, this dissertation describes a targeted and an untargeted (DIA) quantitative proteomic method for the multiplexed absolute quantification of human hepatic DMEs and their applications to developmental pharmacology. Quantification coherence achieved between the targeted and the untargeted proteomic methods was made possible by a newly developed qFASP sample preparation protocol, which allowed quantitative and reproducible recovery of peptides after filter-assisted sample cleanup and protein digestion. These methods are expected to enrich our knowledge regarding ontogenetic changes of human DMEs and establish necessary quantitative information to construct predictive physiologically-based pharmacokinetic models.
en
Copyright held by the author.
Pharmaceutical sciences
Analytical chemistry
Drug-Metabolizing Enzymes
Liquid Chromatography
Mass Spectrometry Quantification
nanoUPLC-Q-TOF Data Independent Acquisition
Quantitative FASP
UPLC-MRM Targeted Proteomics
Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/25430/1/CHEN_ku_0099D_14950_DATA_1.pdf
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CHEN_ku_0099D_14950_DATA_1.pdf.txt
oai:kuscholarworks.ku.edu:1808/216462018-01-31T20:07:51Zcom_1808_1260com_1808_80col_1808_1952col_1808_14157
KU ScholarWorks
advisor
Stobaugh, John F
author
Woods, Joshua
cmtemember
Schöneich, Christian
cmtemember
Lunte, Sue M
cmtemember
Wang, Michael
cmtemember
Dunn, Robert C
2016-10-11T17:04:22Z
2016-10-11T17:04:22Z
2014-12-31
http://dissertations.umi.com/ku:13662
http://hdl.handle.net/1808/21646
The focuses of this dissertation are an examination and advancement of chemistries for the fluorogenic derivatization of the analysis of proquiniodal species. The term proquinoidal species specifically refers to a group of biologically active compounds that easily may be oxidized to the corresponding quinones or imino-quinones. Catechols (Cs), catecholamines (CAs), and 5-hydroxyindoles (5-HIs) are classes of biogenic amines that affect neuroregulatory functions such as mood and appetite. While the determination of these classes of substances has been the accomplished by a variety of techniques over the past several decades, a recent approach has been their conversation to a fluorescent product by use of the fluorogenic reagents benzylamime (BA) or diphenylethylenediamine (DPE). In the first section of this work, a critical examination of these derivatization chemistries is undertaken through product isolation, derivatization kinetics investigations, and yield determination for three substances that represent each analyte class. While not investigated in detail, it is recognized that 3-nitrotyrosine residues in peptides and proteins (a post-translational modification that has been associated with various age related pathologies such as atherosclerosis, neuropathies and others conditions), when reduced to the corresponding 3-aminotyrosine residues, undergo an analogous derivatization reaction to the catechol class. Application of the described derivatization reaction to such substances is an obvious and valuable extension of the present findings. Results obtained from the initial finding indicated that improvements regarding the physical-chemical properties of the DPE and/or BA regents would be highly useful in future applications directed toward the analysis of 3-nitrotyrosine residues, particularly as regards solubility and selective isolation of the formed product. The approach described herein relies on the reduction of the 3-NY residue to the corresponding 3-aminotyrosine (3-AY), with subsequent derivatization by either BA or DPE. Enhancement of the existing derivatization reagents is explored through chemical modification of the reagents through the attachment of various substituents for the purpose of enhanced isolation and/or detection, increasing reagent aqueous solubility, maximization of single production formation, and allowing for the incorporation of stable isotopes. Recognizing that samples of biological origin are present as a complex mixture, further to the alluded to selectivity achieved via reagent design, significant improvements of chromatographic peak capacity were additionally sought. Efforts toward this goal included the fabrication of an Extreme Ultra-Pressure Liquid Chromatography (XUPLC) system, which utilized long columns packed with sub-2µm particles (75 µm id x 0.5-2.0 m L; packed with 1.9 µm BEH C18 particles) necessitating operation at 30,000 psi. An overall goal was the integration of the results obtained from these two differing but complimentary research areas. The derivatization investigations revealed the derivatization reactions to be complete with 2 hours, with yields for Cs of no less than 70% when either reagent, BA or DPE, was utilized. Further reagent design and evaluation efforts were directed toward the characterization of BA and DPE that was elaborated to possess a sulfonic acid moiety, which provided for enhanced aqueous solubility and a selective sample preparation handle via strong anion exchange solid phase extraction. An alternate approach was the elaboration of each base regent to the dimethylamino-analog, again with the motivation being enhanced aqueous solubility but now potentially better electrospray ionization properties for mass spectrometry. Efforts in the XUPLC area revealed the expected gain in resolution and concurrent increased peak capacity. In summary, this dissertation describes advances in the utilization of existing reagents, the preparation and characterization of new reagent analogs and describes an advanced chromatographic system. All of these aspects are expected to be of high valuable in the analytical chemistry of catechol determinations and the related area of 3-nitrotyrosine residues present in peptides and proteins.
en
Copyright held by the author.
Pharmaceutical sciences
Analytical chemistry
Chemistry
3-nitrotyrosine
benzylamine
biogenic amine
derivatization
Fluorogenic Derivatization of Pro-Quinoidal Species: From Biogenic Amines to Protein Bound 3-Nitrotyrosine
Dissertation
URL
https://kuscholarworks.ku.edu/bitstream/1808/21646/1/Woods_ku_0099D_13662_DATA_1.pdf
File
MD5
5950f402329ceed6b263231c4e639a53
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https://kuscholarworks.ku.edu/bitstream/1808/21646/2/Woods_ku_0099D_13662_DATA_1.pdf.txt
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