Synthesis and Characterization of Biodegradable Aromatic Anhydride Copolymers

Aromatic copolyanhydrides based on the common diacids isophthalic acid (IPA), terephthalic acid (TA), 1,3-bis(p-carboxyphenoxy)propane (CPP), and fumaric acid (FA) were synthesized and characterized. The copolymers were highly soluble in chloroform or dichloromethane (>20% w/w) and melted at temperatures between 80 and 130 °C. In comparison, the respective homopolymers are insoluble and melt at temperatures above 250 °C. The copolymers were amorphous and had a weight-average molecular weight between 17 000 and 35 000. The thermal and solubility properties of the aromatic copolymers were dependent upon the copolymer composition. Copolymers of isophthalic acid or fumaric acid containing between 15 and 60 mol % CPP were highly soluble in dichloromethane or chloroform and melted at temperatures below 120 °C. The copolymers containing more than 60% CPP were less soluble and melted at progressively higher temperatures as the fraction of CPP was increased. Copolymers of IPA containing 10-90 % fumaric acid were soluble and melted at temperatures below 100 °C. The copolymers of terephthalic acid, however, were soluble and melted at relatively low temperatures (<100 °C) only in the range of 10-35 % TA content. The hydrolytic degradation of IPA and CPP copolymers was homogeneous with initial release of the IPA monomers and slower erosion of the CPP residues. Increasing the CPP content in the copolymer further slows the degradation and drug release. These polymers were stable upon storage at 25 °C and exposure to 2.5 Mrad of γ-irradiation. Biocompatibility, as compared to implantable polymers currently in clinical use, was good.