IN-VIVO VERSUS IN-VITRO DEGRADATION OF CONTROLLED-RELEASE POLYMERS FOR INTRACRANIAL SURGICAL THERAPY

Intracranial studies to analyze the degradation kinetics of the bioero dible polymer poly[bis(p-carboxyphenoxy)propane-sebacic acid] [p(CPP-S A) 20:80] copolymer wafers were conducted in a rat model. Rats were se parated into four groups: those receiving 1) polymer, 2) polymer loade d with the chemotherapeutic agent BCNU, 3) drug-loaded polymer with pr evious tumor implantation, and 4) polymer and an adsorbable hemostatic material. A polymer wafer was surgically implanted into the brain of each animal. Residual polymer was harvested at varying times for chrom atographic analysis. In vitro effects of pH, mixing, and water availab ility on degradation were also studied. The results of in vitro and in vivo studies were compared to understand the behavior of polymers in a clinical setting. We found that degradation of p(CPP-SA) initially o ccurred more slowly in vivo than in vitro. The presence of BCNU, tumor , and absorbable hemostatic material did not affect the ultimate time of polymer degradation in viva, and the intrinsic polymer degradation time of 1 mm thick p(CPP-SA) 20:80 disks in vivo was 6-8 weeks. (C) 19 94 John Wiley and Sons, Inc.