(543f) A Biodegradable Fiber for Controlled Delivery of Therapeutics to the Eye

Authors: 
Davis, M. E., California Institute of Technology
Wright, K. W., Cedars-Sinai Medical Center


We are developing a pliable biodegradable fiber for controlled release of therapeutics to the eye. We have focused on the delivery of levofloxacin, a potent water-soluble antibiotic. Our goal is to deliver levofloxacin over a one week period, maintaining a tear concentration of at least 1 microgram/ml. Our method involves wet-spinning a fiber from poly(lactide-co-glycolide) and levofloxacin dissolved in dimethylsulfoxide. Fibers are extruded through a syringe into a coagulating bath of water. This method produces soft, flexible fibers that can be implanted near the eye without causing mechanical irritation. We made fibers with many diameters and levofloxacin loading, but have focused on fibers with diameters of 0.2-0.3 mm and drug loadings of 200-350 microgram/in. Initial in-vitro release tests showed burst release, with over 90% of the levofloxacin releasing over the first day. We implanted fibers under the conjunctiva in the inferior fornix of New Zealand white rabbits and found that our target tear concentration was only maintained over the first 48 hours. The fibers were well-tolerated by the rabbits and there were no visible signs of irritation. We have attempted to modify levofloxacin's solubility and release properties by supramolecular interaction with other molecules. Some of these methods have shown potential in-vitro by suppressing burst and controlling the release of levofloxacin. Further in-vivo studies are scheduled for early June. Our method of wet-spinning has also proven to be a general way of creating drug-loaded fibers. We have succeeded in incorporating many different drugs into fibers, including steroidal drugs that could prevent post-operative inflammation.