Sustained Drug Release for Antifibrosis

DESCRIPTION (provided by applicant): Glaucoma is the second leading cause of irreversible vision losss in the United States. Elevated intraocular pressure (IOP) is a significant risk factor for the development of glaucomatous optic neuropathy and visual field loss;1-5 that reduction of the IOP in patients at risk can preserve visual function.6-10 The goal of filtering surgery for glaucoma is the creation and maintenance of a patent fistula to lower IOP and eventually preserving visual function. The major cause of glaucoma filtering surgery failure is external scarring of the conjunctival bleb due to aggressive wound healing.11-12 The use of antifibrosis agents with the intent of limiting fibroblast proliferation at the site of the surgical fistula in eyes, that are presumed to be at a higher risk for failure both during and after the operative procedure, has greatly increased the success of this procedure.13-34 5-fluorouracil and mitomycin are the most commonly utilized agents, however, the former is limited by its short duration of action, which requires repeated administration, whilst the latter has a very narrow margin for over-exposure. Coupling drugs to a bioresorbable vehicle with sustained release capability offers the opportunity for limited, localized delivery to the target tissue during the early post- operative wound healing. The goal of this project is to develop a biocompatible and biodegradable in situ gelable hydrogel system as a carrier of an antifibrosis agent, for more optimally addressing the scar formation issue of filtering surgery. The performance characteristics of the hydrogel formulations will initially be optimized; and the project will be concluded after performing in vivo efficacy evaluations in rabbit glaucoma filtering surgery models. This Phase I SBIR project will set the stage for developing future treatment for antifibrosis. PUBLIC HEALTH RELEVANCE: Glaucoma is the second leading cause of irreversible vision loss in the United States and affects over 70 million people worldwide.35 Glaucoma is controllable if detected early.36 The goal of glaucoma treatment is to reduce intraocular pressure and filtering surgery can be performed to create a patent channel to enable pressure reduction, thereby preserve visual function. The major cause of glaucoma filtration surgery failure is external scarring of the created conjunctival bleb due to aggressive wound healing.11-12 Antifibrosis agents with the intent of limiting scar tissue formation have been utilized both during and after the operative procedure to greatly increase the success of this procedure.13-34 However, the performance of these agents are limited by either a short duration of action or a very narrow margin for over-exposure. Coupling drugs to a bioresorbable vehicle with sustained release capability offers the opportunity for limited, localized delivery to the target tissue during the early post-operative wound healing. The objective of this project is to develop a system for antifibrosis without the need of repeated administration and risk of over-exposure to more optimally address the current obstacle of filtering surgery.