BIOAVAILABILITY OF MICROSPHERE-ENTRAPPED CYCLOSPORINE-A IN THE CORNEAAND AQUEOUS OF RABBITS

Extended release of immunosuppressive drugs and sustained drug levels are desirable for the treatment of corneal graft rejection and other o cular immune disorders. This experiment was conducted with biodegradab le microspheres containing cyclosporine A to assess their suitability for achieving this goal. Microspheres containing cyclosporine A were p repared using a solvent evaporation process. A mixture of poly(lactic) and poly(glycolic) acid polymers (50 : 50) and cyclosporine A was dis solved in a mixture of chloroform and acetone. The solution was then e mulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. The final assayed concentra tion 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 2 4 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 14 4 hours after injection (n = 4 for each group). Corneal levels of cycl osporine 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 micr osphere drug delivery system is an effective means of delivering cyclo sporine A to the cornea and anterior chamber, and may provide an alter native for the treatment of ocular immune disorders.