Biodegradable scleral implant for intravitreal controlled release of fluconazole

Abstract

PURPOSE. To evaluate the feasibility of using a biodegradable polymeric scleral implant containing fluconazole (FLCZ), a bis-triazole antifungal agent, as a potential intravitreal-controlled drug delivery system. METHODS. The scleral implants, loaded with 10, 20, 30, and 50% FLCZ, were prepared with biodegradable polymers of poly (DL-lactide-co-glycolide). Those with all loading doses were used for the in vitro release studies; those with 30% FLCZ were used for the intravitreal release studies in pigmented rabbits. The in vitro and in vivo release rates of FLCZ from the implants were measured periodically with spectrophotometry and high performance liquid chromatography, respectively. The effects of the implants on ocular tissues were evaluated ophthalmoscopically, histologically, and electrophysiologically. RESULTS. The scleral implants loaded with 10, 20, and 30% doses gradually released FLCZ over 4 weeks in vitro; those with 50% FLCZ released most of the drug in one week. FLCZ concentration in the rabbit vitreous remained within the 99% inhibitory concentration for Candida albicans for 3 weeks after implantation. The scleral implant gradually biodegraded, and it disappeared by 4 months after implantation. The electro-physiologic and histopathologic findings demonstrated no substantial toxic reactions in the ocular tissues. CONCLUSION. The current study suggests that a biodegradable, polymeric scleral implant containing FLCZ may be a promising intravitreal drug delivery system to treat fungal endophthalmitis.