Bioavailability of microsphere-entrapped cyclosporine A in the cornea and aqueous of rabbits.

Abstract

Extended release of immunosuppressive drugs and sustained drug levels are desirable for the treatment of corneal graft rejection and other ocular immune disorders. This experiment was conducted with biodegradable microspheres containing cyclosporine A to assess their suitability for achieving this goal. Microspheres containing cyclosporine A were prepared using a solvent evaporation process. A mixture of poly(lactic) and poly(glycolic) acid polymers (50:50) and cyclosporine A was dissolved in a mixture of chloroform and acetone. The solution was then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. The final assayed concentration of cyclosporine A was 15.38 mg/mL. A 0.13 mL aliquot (2.0 mg) of the suspension of the microspheres was injected subconjunctivally in 24 eyes of white New Zealand rabbits. The concentration of cyclosporine A in the aqueous and cornea was measured at 6, 12, 24, 48, 72, and 144 hours after injection (n = 4 for each group). Corneal levels of cyclosporine A ranged from 2392 +/- 70 ng/mL at 6 hours to 1297 +/- 459 ng/mL at 144 hours. The aqueous levels ranged from 110 +/- 0 ng/mL at 6 hours to 62 +/- 11 ng/mL at 144 hours. These data indicate that a microsphere drug delivery system is an effective means of delivering cyclosporine A to the cornea and anterior chamber, and may provide an alternative for the treatment of ocular immune disorders.