Aim: This study was undertaken to investigate the therapeutic efficacy and the toxicity of
the intravitreal biodegradable poly(dl-lactide-co-glycolide)co-polymer microspheres containing
cyclosporin A (CsA-PLGA-MS) on experimental uveitis in rabbits.
Methods: CsA-PLGA-MS that had been prepared by a solvent evaporation approach were
characterized for morphology, particle size, entrapment efficiency, and in vitro release profile
of CsA-PLGA-MS. Therapeutic efficacy of the CsA-PLGA-MS was evaluated by scoring
of the inflammation, aqueous leukocyte counting, aqueous protein determination, and histological
examination in the experimental rabbits with artificial uveitis induced by the injection
of lipopolysaccharide. The toxicity was investigated by slit-lamp examination, indirect
ophthalmoscopy, and electroretinography (ERG) in the noninflamed rabbit eye.
Results: The CsA-PLGA-MS were spherical in shape, with an average particle size of nearly
50 µm and an entrapment efficiency of more than 80%. The compositions of the formulation
that was most effective in the in vivo studies included CsA, PLGA, and 3% Pluronic F68. In vitro released cyclosporine A from the optimized microspheres was approximately 25% during
the 60-day incubation at 37°C. It was demonstrated that the intravitreal injection of the
optimized CsA-PLGA-MS decreased significantly the severity of the inflammatory signs, cellular
infiltrate, aqueous leukocyte counts, and protein levels in the eyes of experimental rabbits
with uveitis, compared to other formulations. Also, the preparation did not cause obvious
toxicity in the noninflamed eyes of rabbits, except that the ERG b-wave amplitude for
the test eyes was reversibly depressed, compared to those of the control eyes at 2 weeks, which
almost recovered at the end of 6 weeks.
Conclusions: The CsA-PLGA-MS preparation might be useful in the treatment of patients
with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.
