In vivo versus in vitro degradation of controlled release polymers for intracranial surgical therapy.
Intracranial studies to analyze the degradation kinetics of the bioerodible polymer poly[bis(p-carboxyphenoxy)propane-sebacic acid] [p(CPP-SA) 20:80] copolymer wafers were conducted in a rat model. Rats were separated into four groups: those receiving 1) polymer, 2) polymer loaded with the chemotherapeutic agent BCNU, 3) drug-loaded polymer with previous tumor implantation, and 4) polymer and an absorbable hemostatic material. A polymer wafer was surgically implanted into the brain of each animal. Residual polymer was harvested at varying times for chromatographic analysis. In vitro effects of pH, mixing, and water availability 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 occurred 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 vivo, and the intrinsic polymer degradation time of 1 mm thick p(CPP-SA) 20:80 disks in vivo was 6-8 weeks.
Wu
M P
MP
Harvard-M.I.T. Division of Health Sciences and Technology, Cambridge 02139.
Tamada
J A
JA
Brem
H
H
Langer
R
R
D000818:Animals; D001673:Biodegradation, Environmental; D001932:Brain Neoplasms / Q000188:drug therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000627:therapeutic use; D002483:Cellulose, Oxidized; D003652:Decanoic Acids / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants; D005549:Foreign-Body Reaction / Q000209:etiology; D018316:Gliosarcoma / Q000188:drug therapy*; D007249:Inflammation; D008297:Male; D011091:Polyesters / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344
D002483:Cellulose, Oxidized; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; C013695:Surgicel; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D002330:Carmustine