FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival

PURPOSE: FK506 has been extensively used in preventing immune rejection for human organ transplantation. This study aimed to evaluate the effects of a biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber for the prolongation of corneal allograft survival in high-risk keratoplasty. METHODS: Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506-PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty rabbits. The graft survival time and clinical features of the FK506-PGLC DDS group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and 0.5% FK506 drops groups. The histopathological examination was performed to evaluate the safety of the FK506-PGLC DDS. RESULTS: The mean graft survival time was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506 concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a sustained release for at least 168 days. No adverse reactions were observed in the FK506-PGLC DDS group. CONCLUSIONS: Biodegradable FK506-PGLC DDS implanted into anterior chamber can effectively prevent immune rejection in high-risk keratoplasty model, presenting a promising approach for the prolongation of corneal allograft survival.