Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactide-co-glycolide) film: in vivo biocompatibility and drug release studies

Bupivacaine-loaded comatrix, formed by bupivacaine-loaded microspheres incl uded in a poly(lactide-co-glycolide) film, was assayed for the controlled r elease of the drug 'in vivo'. The comatrix, with 66.37 mu g of bupivacaine, signifying a dose of 265.5 mu g/kg, was subcutaneously implanted in the ba ck of rats. Maximum plasma bupivacaine concentration was 147.6 +/- 5.0 ng/m l 95 h after the device implantation, and the drug was detected in plasma f or 17 days. The half-life time of bupivacaine improves by more than 50 time s with regard to that of the drug administered in a solution by intraperito neal injection. After 15 days of implantation the comatrix was included in a thin fibrous capsule and degradation of the microspheres was observed. Th e histological studies show good biocompatibility of this comatrix. After 5 0 days the comatrix was degraded and its remains were almost indistinguisha ble from the surrounding tissue. Small number of microspheres was observed and they were surrounded by conjunctive tissue. Nerve packets and small blo od vessels were also observed in the periphery of the implant. (C) 1999 Els evier Science Ltd. All rights reserved.