The overall objective of this project is to develop an injectable or implantable matrix system to provide sustained delivery of therapeutic drugs to the posterior chamber of the eye for treatment of macular degeneration, diabetic retinopathy and other ocular diseases. More effective methods of drug delivery to the posterior segment of the eye are needed for treatment of posterior segment disease. Current ocular drug delivery systems primarily include topical drops, subconjunctival and peribulbar injections, oral administration, intravitreal injections and implants. Each of these delivery routes has significant limitations for posterior drug delivery. Localized drug delivery would be a great advantage in treating posterior segment disease where systemic side effects can be avoided. The sclera of the eye has been found to be permeable to a wide variety of compounds and may be a possible route for local drug delivery. The objectives of the Phase I project are to formulate collagen-based matrices that can be injected or implanted beneath the conjunctiva and to measure the in vitro human scleral permeability of several drugs including dexamethasone, methotrexate, and vancomycin delivered in these systems. The specific aims are to formulate injectable in situ polymerizing collagen solutions and solid collagen matrices containing fluorescein-labeled drugs and to measure the transcleral diffusion of the target drugs using a specially designed perfusion chamber at Emory University. Injectable, in situ polymerizable collagen will be prepared from animal hide as described in U.S. Patent 5,492,135. Solid collagen will be prepared from chemically derivatized collagen by exposing the derivatized collagen to ultraviolet light. Both preparations will be dosed with fluorescein-labeled drugs. Diffusion through human sclera will be measured in the in vitro perfusion chamber (Emory University). Results will be analyzed to determine the most effective matrix system for sustained drug delivery. This system will then be used in Phase II studies in animal models.
Thesaurus Terms: biomaterial development /preparation, collagen, drug delivery system, polymer, sclera conjunctiva, dexamethasone, diabetic retinopathy, macular degeneration, membrane permeability, methotrexate, vancomycin SDS polyacrylamide gel electrophoresis, bioengineering /biomedical engineering, calorimetry, fluorescein, human tissue, medical implant science
