There is a growing subset of wet age-related macular degeneration (AMD) patients who do not fully respond to standard of care treatment, which... Show moreThere is a growing subset of wet age-related macular degeneration (AMD) patients who do not fully respond to standard of care treatment, which consists of bimonthly/monthly bolus intravitreal injections of anti-vascular endothelial growth factors (anti-VEGFs). Some of these patients may respond to a combination therapy of anti-VEGF and corticosteroids. One treatment option uses a dexamethasone implant that releases for six months. This regimen, however, requires both the bimonthly/monthly intravitreal injections of anti-VEGF and semiannual intravitreal injections of the dexamethasone implant. Combining the two treatments into a single drug delivery system (DDS) would reduce the total number of injections, reducing the risk of potential complications (endophthalmitis, retinal detachment, intravitreal hemorrhage, increased intraocular pressure, and cataract) as well as the socioeconomic burden of treatment.The overarching goal of this study was to develop a single DDS that simultaneously releases anti-VEGF (aflibercept) and corticosteroid (dexamethasone) for the treatment of non-responsive wet AMD patients. Our laboratory previously developed a thermoresponsive, biodegradable microparticle-hydrogel DDS that releases anti-VEGF over a period of six months. The aims of the study were to (1) modify this system to include dexamethasone-loaded nanoparticles, optimize release kinetics for both drugs, and characterize the DDS; (2) evaluate the in vivo treatment efficacy in a laser-induced choroidal neovascularization (CNV) model; and (3) investigate the impacts of temperature and storage on the DDS integrity. Show less
