Current U.S. Food and Drug Administration (FDA)-approved drug therapies for choroidal neovascularization (CNV) secondary to age-related... Show moreCurrent U.S. Food and Drug Administration (FDA)-approved drug therapies for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), also known as wet AMD, require monthly or bimonthly intravitreal (IVT) injections of bolus antiangiogenic agents such as anti-vascular endothelial growth factors (anti-VEGFs) [1]. Less-frequent administration of anti-VEGFs via controlled and extended release is needed to lower the socio-economic impact and lessen the potential side-effects associated with frequent IVT injections. While a controlled delivery system is beneficial, the challenges of initial burst (IB), maintenance of drug bioactivity, and understanding the drug distribution in the diseased eye must be addressed to design an optimal system to address this need. The main goal of this study was to develop a drug delivery system (DDS) capable of delivering anti-VEGF for six months. Additionally, we propose that controlled and extended release of anti-VEGF will yield a greater reduction in CNV growth compared to bolus administration of the same drug. Thus, the current monthly/bimonthly treatment regimen could be replaced by, say, a semi-annual treatment. To accomplish this goal, three specific aims were performed: 1) Development of an injectable microsphere-hydrogel DDS with minimal IB and prolonged release of bioactive anti-VEGF; 2) Verification and validation of the efficacy of said DDS in vivo; and 3) A proof-of-concept finite element analysis comparing the drug distribution throughout a diseased eye to that of a healthy eye. Ph.D. in Biomedical Engineering, July 2015 Show less
