A biodegradable ophthalmic drug delivery device

DESCRIPTION (provided by applicant): Our long-term research goal is to develop an ophthalmic, nanofiber-based, biodegradable device that will provide extended release of therapeutic agents to the posterior segment of the eye via transscleral and intravitr eal approaches. This platform device will address the major technical problem in the treatment of posterior eye diseases (diabetic retinopathy, macular degeneration, and posterior uveitis), which is the need for repeated injections or long-term implantatio n of therapeutic agents with significant side effects. The specific aims of this Phase I project are to determine 1) which combinations and concentrations of poly(lactide-co-glycolide) (PLGA) with triamcinolone acetonide and budesonide produce a structural ly stable nanofiber composite material under dry and wet conditions; 2) the in vitro rate of drug elution from samples; 3) the effect of ethylene oxide sterilization on the drug-nanofiber mat samples; and 4) the in vitro biocompatibility of samples with hu man ocular epidermal keratinocytes and retinal pigment epithelial cells. The results of Phase I will be used to carry promising nanofiber PLGA-ophthalmic drug combinations forward to Phase II laboratory in vivo studies with the ultimate goal of an efficaci ous, safe, and commercially successful treatment option for the aging population with posterior eye diseases. There is tremendous market potential for a nanofiber-based, biodegradable sustained release corticosteroid delivery platform. Diabetic macular ed ema (DME) is a primary cause of decreased vision in diabetic retinopathy, which is the number one cause of vision loss in the working age population in the U.S. and the western world. The estimated market potential for DME is estimated to be 1 Billion in the U.S. by 2013. Uveitis is a low frequency, high severity ocular disease which causes about 10% of blindness in the U.S. Posterior uveitis and macular edema are commonly treated with periocular and intravitreal injections. An intermediate-term (semi-annu al), biodegradable corticosteroid implant with high potency and lower side effect profile is a very attractive alternative to repeated injections and available non-absorbed implanted devices. Corticosteroids are also being evaluated for treatment of wet ma cular degeneration (AMD) and vascular occlusive diseases. A prospective, multi-center National Eye Institute (NEI) trial is underway evaluating triple therapy using intravitreal triamcinolone and bevacizumab with photodynamic therapy for wet macular degene ration (VERTACL). PUBLIC HEALTH RELEVANCE: The exudative macular edema common to DME, uveitis, and AMD is a leading cause of blindness in the western world. The aim of this project is to develop a novel electrospun corticosteroid-laden, nanofiber-based dr ug delivery device. The successful completion of this project will reduce the morbidity and costs associated with ocular drug delivery, as well as improve vision loss in these common posterior segment diseases.