Browsing Theses and Dissertations by Subject "Nanomedicine"
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DEVELOPMENT AND CHARACTERIZATION OF POLYMER-OIL NANOSTRUCTURED CARRIER (PONC) FOR CONTROLLED DELIVERY OF ALL-TRANS RETINOIC ACID (ATRA)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.
TAILORING DRUG-CARRIER INTERACTIONS IN POLY(SIALIC ACID) MICELLES FOR USE AS CANCER THERAPEUTIC CARRIERSAlthough great progress has been made, cancer still remains one of the most prevalent maladies plaguing mankind. New treatment methodologies using nanoparticles have come to the forefront by allowing for enhanced delivery of therapeutics to the tumor site. The design of the nanoparticle should allow for long circulation times, tumor-specific targeting and efficient release at the site of action. This requires that both the external shell and internal core of the nanoparticle be carefully selected to meet the maximal criteria of each of these steps. Poly(sialic acid) (PSA), a naturally occurring polysaccharide, meets all of the benchmarks of an effective exterior coating yet remains relatively unexplored in the field of drug delivery. Due to stealth properties, natural tumor targeting ability, and inherent pH-responsive elements, PSA has frequently been viewed as a “next-generation” surface coating. Just as important, the internal composition of the carrier should aid in effective drug loading but also rapid release. The selection of the core containing groups as well as therapeutic should be maximized in order to customize the carrier to drug. Here, we have developed PSA micelles composed of various internal groups selected to maximize drug loading and facilitate release. Loading of the chemotherapeutic doxorubicin was optimized through variations in non-covalent bonding forces between drug and carrier. Furthermore, PSA micelles composed of internal pH-responsive groups of varying hydrophobicity were also developed to tailor micelle swelling points at conditions analogous towards those found upon cellular uptake. Both of these were effective delivery platforms towards MCF-7 human breast adenocarcinoma cells.