Chemical changes during in vivo degradation of poly(anhydride-imide) matrices

Abstract

The in vivo degradation characteristics of a novel class of biodegradable polymers, poly(anhydride-imides), were investigated. The poly(anhydride-imides) examined were poly[trimellitylimidoglycine-co-1,6-bis(p-carboxyphenoxy)hexane] (TMA-gly:CPH) in 10:90, 30:70 and 50:50 molar ratios and poly[pyromellitylimidoalanine-co-1,6-bis(p-carboxyphenoxy)hexane] (PMA-ala:CPH) in 10:90 and 30:70 molar ratios. The polymer matrices were compression-molded into circular discs, then implanted in rat subcutaneous tissues for nearly two months. At defined time intervals, the animals were sacrificed and explants analyzed. Proton NMR spectroscopic analysis revealed a complete absence of imide monomer units in PMA-ala:CPH compositions after 28 d and complete removal of imide units at 56 d from TMA-gly matrices. Gross observation of the implants closely correlated to the imide content: with decreasing imide content, the explants darkened and fragmented at a faster rate. The chemical compositions of the poly(anhydride-imide) explants were also monitored using IR spectroscopy. The residual amount of anhydride bonds in the polymer backbone following implantation were calculated from peaks specific to the anhydride bonds relative to the total amount of carbonyl bonds present. Initially, the imide (TMA-gly or PMA-ala) anhydride bonds were rapidly hydrolyzed then solubilized, followed by the slower hydrolysis of the CPH monomer anhydride bonds.