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    • School of Graduate Studies (UMKC)
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    • 2010 Dissertations (UMKC)
    • 2010 UMKC Dissertations - Freely Available Online
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    Fomulation and Delivery of Drugs for Macular Edema and Retinoblastoma; Synthesis and In Vitro Characterization of Doxorubicin Loaded Surface Modified Nanoparticles Using PLGA-PEG-PLGA Polymer

    Boddu, Sai Hanuman Sagar, 1981-
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    [PDF] BodduForDelDruMac.pdf (6.323Mb)
    Date
    2011-01-20
    2010
    Format
    Thesis
    Metadata
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    Abstract
    Macular edema (ME) is caused by central extravascular swelling of the macula resulting in a significant loss of visual activity. Corticosteroids are widely used in the treatment of ME. In this project, nanoparticles of dexamethasone (DEX), hydrocortisone acetate (HA) and prednisolone acetate (PA) were developed and characterized for size, shape, polydispersity, and in vitro release. Further the effect of PLGA-PEG-PLGA thermosensitive gel on the release mechanisms of steroids from PLGA nanoparticles was also studied. Release from nanoparticles suspended in thermosensitive gels followed zero-order kinetics with no apparent burst effect. Ex vivo permeability studies further confirmed sustained release of DEX from nanoparticles suspended in thermosensitive gels. Retinoblastoma (RB) represents a common form of intraocular malignancy affecting the retina. Recent work has explored the systemic/intravitreal administration of topotecan, etoposide, carboplatin and vincristine for the treatment of RB. However, the current therapy is associated with non-specific toxicity and patient non-compliance. An attempt was made to develop and evaluate a novel folate receptor targeted and sustained drug delivery system for RB cells using doxorubicin (DOX) as a model drug. Uptake of DOX was approximately four times higher with DOX-loaded PLGA-PEG-FOL micelles (DOXM) than DOX in Y-79 cells over-expressing folate receptors. Dispersion of DOXM in PLGA-PEG-PLGA gel sustained drug release over a period of two weeks. Nanoparticles are colloidal particulate systems widely employed in targeted delivery of drugs to cancer cells. In this project, a novel strategy was proposed for the synthesis of folate conjugated nanoparticles for both hydrophilic and hydrophobic drug molecules using PLGA-PEG-FOL polymer. Nanoparticles were evaluated for the entrapment efficiency, morphology, particle size and in vitro release. Presence of folate on the nanoparticle surface was confirmed by using 1HNMR and TEM studies. Quantitative uptake and cell viability studies were carried out in folate receptor-positive ovarian cancer (SKOV3) cells. Folate conjugated nanoparticles (size ~200 nm) were successfully prepared using single (O/W) and double emulsion (W/O/W) methods. Folate conjugated nanoparticles exhibited higher uptake and cytotoxicity in SKOV3 cells in comparison with the pure DOX and unmodified nanoparticles.
    Table of Contents
    Abstract -- Illustrations -- Tables -- Acknowledgments -- Introduction -- Rationale for Investigation -- Novel Nanoparticulate Gel Formulations of Steroids for the Treatment of Macular Edema -- Rationale for Investigation -- In Vitro Evaluation of a Targeted and Sustained Release System for Retinoblastoma Cells Using Doxorubicin as a Model Drug -- Rationale for Investigation -- Synthesis and In-Vitro Characterization of Doxorubicin Loaded Surface Modified Nanoparticles Using PLGA-PEG-FOL Polymer -- Summary and Recommendations -- Appendix -- References -- Vita.
    URI
    http://hdl.handle.net/10355/9588
    Degree
    Ph.D
    Thesis Department
    Pharmacy (UMKC)
     
    Chemistry (UMKC)
     
    Collections
    • 2010 UMKC Dissertations - Freely Available Online
    • Pharmaceutical Sciences Electronic Theses and Dissertations (UMKC)
    • Chemistry Electronic Theses and Dissertations (UMKC)

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