Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis.

Abstract

PURPOSE: The purpose was to evaluate the efficacy of the intravitreal implantation of the biodegradable cyclosporin A (CsA) drug delivery system (DDS) for experimental chronic uveitis. METHODS: The DDS was prepared by formulating CsA into glycolide-co-lactide-co-caprolactone copolymer (PGLC). Right eyes of 30 New Zealand white rabbits were used to establish a model of uveitis and randomized into control, intravitreal non-medicated DDS, oral CsA (15 mg/kg daily), and intravitreal CsA-PGLC DDS (each containing 2 mg CsA) groups. The progress of ocular inflammation, results of electroretinography, and histopathological examination of ocular, renal, and hepatic functions were recorded. Intravitreal CsA levels were measured in another 13 rabbits receiving an implant of the CsA-PGLC DDS. RESULTS: Chronic uveitis was successfully induced in all 30 eyes. The inflammation in the eyes with no treatment, non-medicated implant, and oral CsA was more severe than those with the CsA-PGLC DDS at each timepoint. The electroretinography b-wave was depressed much less in the CsA-PGLC DDS group than in the other three groups (p<0.05). No renal or hepatic tissue damage was found in eyes with the CsA-PGLC DDS. The mean intravitreal CsA level was 102.2~145.5 ng/ml at 1~3 weeks after CsA-PGLC DDS implantation, 491.0~575.2 ng/ml at 4~10 weeks, and 257.3 ng/ml at 14 weeks; no toxicity was detected. CONCLUSION: Intravitreal implantation of the biodegradable CsA-PGLC DDS may effectively reduce the intraocular inflammation in rabbits with no toxicity, which provides a potentially safe and convenient approach for the treatment of chronic uveitis.