Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration

Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1? inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.