Development and evaluation of novel in situ depot-forming controlled release formulations

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Development and evaluation of novel in situ depot-forming controlled release formulations

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/11939

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dc.contributor.advisor Mitra, Ashim K., 1954- en
dc.contributor.author Mishra, Gyan Prakash
dc.date.accessioned 2011-10-24T18:59:40Z
dc.date.available 2012-10-24T11:15:06Z
dc.date.issued 2011-10-24
dc.date.submitted 2011 Fall en
dc.identifier.uri http://hdl.handle.net/10355/11939
dc.description Title from PDF of title page, viewed on October 24, 2011 en
dc.description Dissertation advisor: Ashim K. Mitra en
dc.description Vita en
dc.description Includes bibliographical references (p. 164-176) en
dc.description Thesis (Ph.D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2011 en
dc.description.abstract Controlled 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.tableofcontents Literature 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 recommendations en
dc.format.extent xv, 177 pages en
dc.language.iso en_US en_US
dc.publisher University of Missouri--Kansas City en
dc.subject.lcsh Drug delivery systems en
dc.subject.lcsh Eye -- Diseases -- Treatment en
dc.subject.mesh Drug Delivery Systems en
dc.subject.mesh Eye Diseases -- drug therapy en
dc.subject.other Dissertation -- University of Missouri--Kansas City -- Pharmacy en
dc.subject.other Dissertation -- University of Missouri--Kansas City -- Chemistry en
dc.title Development and evaluation of novel in situ depot-forming controlled release formulations en_US
dc.type Thesis en_US
thesis.degree.discipline Pharmaceutical Sciences and Chemistry en
thesis.degree.grantor University of Missouri--Kansas City en
thesis.degree.name Ph.D. en
thesis.degree.level Doctoral en


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