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Targeted Drug Delivery To Leukocytes with ICAM-1 Derived Peptides
dc.contributor.advisor | Siahaan, Teruna J. | |
dc.contributor.author | Majumdar, Sumit | |
dc.date.accessioned | 2008-09-29T05:40:41Z | |
dc.date.available | 2008-09-29T05:40:41Z | |
dc.date.issued | 2008-07-15 | |
dc.date.submitted | 2008 | |
dc.identifier.other | http://dissertations.umi.com/ku:2637 | |
dc.identifier.uri | http://hdl.handle.net/1808/4243 | |
dc.description.abstract | Intercellular adhesion molecule-1 (ICAM-1) derived cyclic peptide cIBR [cyclo(1,12)PenPRGGSVLVTGC] showed high affinity for leukocyte function associated antigen-1 (LFA-1) receptor and was internalized into the MOLT-3 T-cells. Therefore, the objective of the dissertation was to explore the possibility of selectively delivering drugs to leukocytes using ICAM-1 derived peptides. Fluorescein isothiocyanate conjugated cIBR (FITC-cIBR) and doxorubicin conjugated cIBR (DOX-cIBR) entered the HL-60 cells by receptor mediated endocytosis and passive diffusion, respectively. High hydrophobicity of DOX-cIBR was proposed to be responsible for its energy-independent entry (chapter 2). To check the effect of hydrophobicity on internalization, two relatively more hydrophilic cIBR-derived peptides were conjugated to DOX. However, both the DOX-peptide conjugates were internalized passively (chapter 3). Degradation mechanism of methotrexate conjugate of cIBR (MTX-cIBR) was studied and suitable formulation conditions were developed. Stability of MTX-cIBR was assessed with in vitro biological matrices to determine optimum dosing regimen for in vivo studies (chapter 4). | |
dc.format.extent | 185 pages | |
dc.language.iso | EN | |
dc.publisher | University of Kansas | |
dc.rights | This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author. | |
dc.subject | Pharmaceutical chemistry | |
dc.title | Targeted Drug Delivery To Leukocytes with ICAM-1 Derived Peptides | |
dc.type | Dissertation | |
dc.contributor.cmtemember | Siahaan, Teruna J. | |
dc.contributor.cmtemember | Audus, Kenneth L. | |
dc.contributor.cmtemember | Krise, Jeffrey P. | |
dc.contributor.cmtemember | Berkland, Cory J. | |
dc.contributor.cmtemember | David, Sunil A. | |
dc.thesis.degreeDiscipline | Pharmaceutical Chemistry | |
dc.thesis.degreeLevel | PH.D. | |
kusw.oastatus | na | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
kusw.bibid | 6599467 | |
dc.rights.accessrights | openAccess |