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    DEVELOPMENT AND CHARACTERIZATION OF POLYMER-OIL NANOSTRUCTURED CARRIER (PONC) FOR CONTROLLED DELIVERY OF ALL-TRANS RETINOIC ACID (ATRA)

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    TETDEDXNarvekar-temple-0225E-1 ...
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    Genre
    Thesis/Dissertation
    Date
    2014
    Author
    Narvekar, Mayuri
    Advisor
    Wong, Ho-Lun
    Committee member
    Borenstein, Michael R.
    Lebo, David
    Shoyele, Sunday
    Department
    Pharmaceutical Sciences
    Subject
    Pharmaceutical Sciences
    Nanotechnology
    All-trans Retinoic Acid
    Controlled Drug Delivery
    Nanomedicine
    Plga
    Poorly Water Soluble Drugs
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/3331
    
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    DOI
    http://dx.doi.org/10.34944/dspace/3313
    Abstract
    The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.
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