Bioerodible polyanhydrides as drug-carrier matrices. II. Biocompatibility and chemical reactivity

Abstract

The biocompatibility of bioerodible polyanhydrides and toxicology of the polymer breakdown products were assessed. Poly-[bis (p-carboxy-phenoxy) propane anhydride] (PCPP), Poly(terephthalic acid anhydride) (PTA), and their copolymers with sebacic acid were tested. The polymers did not provoke inflammatory responses in the corneas of rabbits over a six week implantation period. Subcutaneous implantation studies of PCPP in rats over a six month period showed no evidence of inflammatory cells and only slight tissue encapsulation by layers of fibroblastic cells. The degradation products of the polymers were nonmutagenic, noncytotoxic, and had a low teratogenic potential. The in vitro growth of mammalian cells on the polymers was unaffected as measured by cell morphology and cell growth rate. The chemical reactivity of the polyanhydrides with reactive model drugs, para substituted anilines, was also examined. Amides were formed when the drugs were injection molded with the polyanhydrides at 120 degrees C. However, no reaction was observed using compression molding at room temperature. No reaction occurred between the polymer and the drug during the hydrolytic degradation of the matrix at 37 degrees C.