Current standard of care for neovascular age-related macular degeneration (AMD) requires repeated intravitreal bolus injections of anti... Show moreCurrent standard of care for neovascular age-related macular degeneration (AMD) requires repeated intravitreal bolus injections of anti-vascular endothelial growth factors (anti-VEGFs). This frequent repeated injection regimen present increased risks of potential complications including endophthalmitis, retinal detachment, intravitreal hemorrhage, and cataract. In addition, pharmacokinetic profiles of drugs are non-optimal, since the peak level of drug after bolus injections may cause potential toxic effect while the quick clearance later may render subtherapeutic concentration. Finally, the significant socioeconomic burden upon patients, family, and healthcare systems cannot be ignored. Therefore, a controlled delivery system for anti-VEGF drugs is in high demand to reduce injection frequencies, minimize potential risks, and improve efficacy.The overall goal of this study was to develop a biodegradable and injectable drug delivery system (DDS) capable of releasing therapeutic anti-VEGF (aflibercept) for six months. Based on our previous non-degradable DDS for anti-VEGFs, this work sought to introduce biodegradable polymeric crosslinker into the hydrogel matrix to make the DDS biodegradable. To accomplish this goal, three specific aims were pursued: (1) Development of a biodegradable and injectable microsphere-hydrogel DDS for controlled release of aflibercept for six months, important biomaterial parameters including thermoresponsive behavior, injectability, in vitro degradation and biocompatibility, release kinetics, and drug bioactivity were characterized to obtain the optimal DDS formulation; (2) Evaluation of long-term in vivo efficacy of aflibercept-loaded DDS in laser-induced CNV model; (3) Investigation of in vivo safety and biocompatibility of DDS injection and its degradation products. Show less
