Chitosan microspheres in PLG films as devices for cytarabine release

Cytarabine was included in chitosan microspheres and several of these micro spheres were embedded in a poly(lactide-co-glycolide) (PLG) film to constit ute a comatrix system, to develop a prolonged release form. Chitosan micros pheres, in the range of 92 +/- 65 mu m, having good spherical geometry and a smooth surface incorporating cytarabine, were prepared. The cytarabine am ount included in chitosan microspheres was 43.7 mu g of ara-C per milligram microsphere. The incorporation efficiency of the cytarabine in microsphere s was 70.6%. Total cytarabine release from microspheres in vitro was detect ed at 48 h. Inclusion of cytarabine-loaded microspheres in poly(lactide-co- glycolide) film initiated a slower release of the drug and, in this way, th e maximum of cytarabine released (80%) took place in vitro at 94.5 h. Comat rices, with 8.7 mg of cytarabine, signifying a dose of 34.5 mu g/kg, were s ubcutaneously implanted in the back of rats. Maximum plasma cytarabine conc entration was 18.5 +/- 1.5 mu g/ml, 48 h after the device implantation and the drug was detected in plasma for 13 days. The histological studies show a slow degradative process. After 6 months of implantation, most of the mic rospheres of the matrix seemed to be intact, the comatrix appeared surround ed by conjunctiva tissue and small blood vessels and nerve packets were det ected in the periphery of the implant. (C) 2000 Elsevier Science B.V. All r ights reserved.