Biodegradable poly(ether-ester) multiblock copolymers for controlled release applications: An in vivo evaluation

Abstract

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate segments were evaluated for their in vivo degradation and biocompatibility in order to establish a correlation with previously reported in vitro results. Porous polymer sheets were implanted subcutaneously for 32 weeks in rats. The degradation was monitored visually (histology), by molecular weight (GPC), and by copolymer composition (NMR). Substitution of the aromatic terephthalate units by aliphatic succinate units was shown to accelerate the degradation rate of the copolymers. Direct correlation of the in vivo and in vitro degradation of the porous implants showed a slightly faster initial molecular weight decrease in vivo. Besides hydrolysis, oxidation occurs in vivo due to the presence of radicals produced by inflammatory cells. In addition, the higher molecular weight plateau of the residue found in vivo indicated a higher solubility of the oligomers in the extracellular fluid compared to a phosphate buffer. Minor changes in the poly(ether-ester) compositions were noted due to degradation. Microscopically, fragmentation of the porous implants was observed in time. At later stages of degradation, macrophages were observed phagocytozing small polymer particles. Both in vitro cytotoxicity studies and histology on in vivo samples proved the biocompatibility of the poly(ether-ester)s.