Injectable Absorbable Ocular Inserts for Controoled Drug Delivery

It is recognized that delivery of drugs to retina at therapeutic levels through systemic or topical administration is impossible in most cases and blood retinal barrier prevents penetration of many systemic drugs into the retina. For this contemporary investigators focusing on the treatment of cytomegalovirus (CMV) retinitis and chronic uveitis used a non-absorbable intravitreal implant for controlled delivery of ganciclovir and cyclosporine, respectively. To deal with this more broadly, a minimally less invasive procedure using a novel injectable dosage form, requiring no post-surgical implant removal is evoked. Thus, the objective of Phase I is to determine the feasibility of using novel gel-forming, injectable absorbable polymers for controlled intra-ocular delivery of key drugs. Phase I entails (1) preparing and characterizing of several candidate gel formers and screening their formulations with pilocarpine (for glaucoma) and a model diagnostic drug, naproxen (an anti-inflammatory), ganciclovir (for CMV retinitis) and cyclosporine (for chronic uveitis) through an in vitro release study to identify suitable matrices for a subsequent in vivo study; (2) conducting an in vivo study with pilocarpine in a selected gel former as subconjunctival and intravitreal gel inserts to determine effect of administration site on drug pharmacokinetics; (3) conducting pilot in vivo study on intravitreally injected formulations of the above four drugs in rabbits; and (4) analyzing in vitro results and selecting the most promising system for detailed in vivo, development, and safety studies in Phase II. Phase I data will be used to determine feasibility of using novel injectable formulations to deliver effectively four major drug types intra-ocularly, particularly to the retina- Short-term outcome of a successful Phase I is development of at least one delivery system for treatment of retinal lesions or inflammation. Long-term impact will be availability of a novel, minimally invasive approach for effective treatment of chronic uveitis and CMV retinitis at a physician's office.