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dc.contributor.authorHirani, Anjali A.en_US
dc.date.accessioned2016-10-22T06:00:36Z
dc.date.available2016-10-22T06:00:36Z
dc.date.issued2015-04-30en_US
dc.identifier.othervt_gsexam:4941en_US
dc.identifier.urihttp://hdl.handle.net/10919/73318
dc.description.abstractAge-related macular degeneration (AMD) is one of the leading causes of blindness in adults over the age of 60. Currently, at least 11 million patients in the United States have some form of macular degeneration and this number is projected to grow as the population ages. The more severe form of the disease – neovascular (wet) AMD, is characterized by intraocular neovascularization, inflammation, and retinal damage; however, the disease progression can be deterred through intraocular injections of anti-angiogenic agents. The complications and burden that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this an interesting territory for the development of novel drug delivery systems. New methods for drug delivery are being investigated exploring the use of nanoparticles and other polymeric materials. The goal of this project is to study the potential use of poly(lactide-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles in thermoreversible gels as localized sustained intraocular drug delivery. We prepared stable and reproducible corticosteroid-encapsulated nanoparticles in thermoreversible gels to inhibit vascular endothelial growth factor (VEGF) overexpression characteristic of neovascular AMD. We characterized the drug delivery system by obtaining size, shape, and drug encapsulation data. We also demonstrated that the polymer could be injected into the vitreous as a solution and transition to a gel phase based on the temperature difference between regular indoor environment and the vitreous body. The drug delivery system was tested on human retinal pigment epithelial cells (ARPE-19), for cytotoxicity, uptake and VEGF expression. We also examined the drug delivery system's ability to mitigate the disease progression in a mouse model of choroidal neovascularization (CNV). The effect on blood vessel area was shown and the changes in the mRNA expression of angiogenesis mediators were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). These results indicate that the proposed drug delivery systems has the promise to be developed for retinal diseases, involving CNV, including neovascular AMD. Further studies are warranted in developing this promising intraocular drug delivery system for wet AMD and similar ophthalmic diseases.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis Item is protected by copyright and/or related rights. Some uses of this Item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjectChoroidal Neovascularizationen_US
dc.subjectAge-Related Macular Degenerationen_US
dc.subjectSustained Drug Deliveryen_US
dc.titleCorticosteroid-Encapsulated Nanoparticles in Thermoreversible Gels for the Amelioration of Choroidal Neovascularization in Age-Related Macular Degenerationen_US
dc.typeDissertationen_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical Engineeringen_US
dc.contributor.committeechairLee, Yong Wooen_US
dc.contributor.committeechairAchenie, Luke E. K.en_US
dc.contributor.committeememberLi, Liwuen_US
dc.contributor.committeememberGoldstein, Aaron S.en_US
dc.contributor.committeememberPathak, Yashwanten_US
dc.contributor.committeememberSutariya, Vijaykumar B.en_US


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