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dc.contributor.advisorMitra, Ashim K., 1954-en
dc.contributor.authorMishra, Gyan Prakash
dc.date.issued2011-10-24
dc.date.submitted2011 Fallen
dc.descriptionTitle from PDF of title page, viewed on October 24, 2011en
dc.descriptionDissertation advisor: Ashim K. Mitraen
dc.descriptionVitaen
dc.descriptionIncludes bibliographical references (p. 164-176)en
dc.descriptionThesis (Ph.D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2011en
dc.description.abstractControlled drug delivery utilizing novel biodegradable and biocompatible pentablock copolymers could be a valuable strategy for the treatment of chronic eye diseases. In attempts to achieve controlled drug release, various approaches were evaluated which eventually resulted in the development of novel polymeric material and a delivery system. Poly (ethylene glycol)-poly (ε-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG) thermosensitive hydrogel was employed for sustained drug delivery. A polymeric additives strategy was selected based on the property to provide better packing through intra- and intermolecular interactions between the triblock polymeric chains of the hydrogel matrix. PCL was selected as a hydrophobic additive and polyvinyl alcohol (PVA) as a hydrophilic additive, respectively. The additives strategy was found to modulate the sol-gel transition and drug release kinetics from the hydrogel. The effect of PCL on the sol-gel transition was more pronounced than PVA. However, PVA played a dominant role in regulating drug release kinetics, whereas no significant difference in drug release was observed with PCL. To accelerate the degradation rate of highly crystalline and hydrophobic PCL block we have successfully synthesized pentablock polymers based thermosensitive hydrogel by incorporating PLA block in the center of PEG-PCL-PEG. These polymers were characterized by 1H NMR, GPC, and FT-IR. The effect of block composition on the sol-gel transition, crystallinity, and drug release kinetics was studied. The release kinetics of hydrophobic drug was easily modulated by altering the hydrophobic block segment. Moreover, the effect of block composition on the sol-gel transition was evaluated. A specific combination of molecular weight and block ratio of pentablock copolymer can be utilized for nanoparticles preparation. We have also successfully polymerized PCL with PEG and faster degrading blocks such as polyglycolic acid and and polylactic acid for the preparation of nanoparticles. Nanoparticles alone demonstrate initial burst release due to surface adsorbed drug molecule. A final composite formulation based approach (nanoparticles suspended in thermosensitive gel) minimized the burst release of drug and resulted in continuous nearly zero order drug release. Pentablock copolymers also resulted in a negligible release of inflammatory mediators in different cell lines. Therefore, we have successfully developed a novel biomaterial for controlled drug delivery.en_US
dc.description.tableofcontentsLiterature review -- Introduction -- Effect of hydrophobic and hydrophilic additives on sol-gel transition and release behavior of timolol maleate from polycaprolactone based hydrogels -- Synthesis and characterization of novel thermosensitive pentablock hydrogels for controlled drug delivery -- Synthesis and characterization of different pentablock copolymer compositions in the preparation of nanoparticles -- Evaluation of different pentablock copolymer compositions biocompatibility utilizing various cell lines -- Development and evaluation of composite formulations of nanoparticles suspended in thermosensitive hydroges -- Summary and recommendationsen
dc.format.extentxv, 177 pagesen
dc.identifier.urihttp://hdl.handle.net/10355/11939
dc.publisherUniversity of Missouri--Kansas Cityen
dc.subject.lcshDrug delivery systemsen
dc.subject.lcshEye -- Diseases -- Treatmenten
dc.subject.meshDrug Delivery Systemsen
dc.subject.meshEye Diseases -- drug therapyen
dc.subject.otherDissertation -- University of Missouri--Kansas City -- Pharmacyen
dc.subject.otherDissertation -- University of Missouri--Kansas City -- Chemistryen
dc.titleDevelopment and evaluation of novel in situ depot-forming controlled release formulationsen_US
dc.typeThesisen_US
thesis.degree.disciplinePharmacyeng
thesis.degree.disciplineChemistryeng
thesis.degree.grantorUniversity of Missouri--Kansas Cityen
thesis.degree.levelDoctoralen
thesis.degree.namePh.D.en


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