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    Targeted Drug Delivery To Leukocytes with ICAM-1 Derived Peptides

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    umi-ku-2637_1.pdf (5.645Mb)
    Issue Date
    2008-07-15
    Author
    Majumdar, Sumit
    Publisher
    University of Kansas
    Format
    185 pages
    Type
    Dissertation
    Degree Level
    PH.D.
    Discipline
    Pharmaceutical Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    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).
    URI
    http://hdl.handle.net/1808/4243
    Collections
    • Dissertations [4472]
    • Pharmaceutical Chemistry Dissertations and Theses [141]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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