Clearance of microsphere-entrapped 5-fluorouracil and cytosine arabinoside from the vitreous of primates.

Experiments were conducted with biodegradable microspheres containing antimetabolites to assess the release of the drugs from the microspheres into the vitreous cavity of primates. Microspheres containing a mixture of radiolabeled and cold cytosine arabinoside (Ara-C) or 5-fluorouracil (5-FU) were prepared using a solvent evaporation process. The copolymers of poly (lactic) and poly (glycolic) acid (85:15) and drug was dissolved in a mixture of chloroform and acetone. The solutions were then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. A 0.1 mL aliquot of a suspension of the microspheres was then injected into one eye of eight African Green monkeys. Half received 250 +/- 10 micrograms of Ara-C and the others 375 +/- 15 micrograms of 5-FU. The concentration in the vitreous was then measured by removing a 0.1 mL sample of vitreous at 1, 2, 4 and 11 days after injection. Both drugs released from microspheres were still detectable in the eye 11 days after injection and the clearance kinetics were similar for both drugs. The results indicate that the microspheres appear promising as a slow drug-delivery system for future investigations in conjunction with these and other antimetabolites suitable for the treatment of PVR.