Biodegradable Multiblock Copolymers for Drug Delivery Applications

Microspheres of a hydrophobic and a hydrophilic poly(ether-ester) copolymer were evaluated for their in-vitro and in-vivo biocompatibility and degradation. The microspheres prior to and after sterilization were tested for in-vitro cytotoxicity. The invivo biocompatibility of the poly(ethylene glycol) terephthalate and poly(butylene terephthalate) (PEGT/PBT) microspheres was evaluated subcutaneously and intramuscularly for 24 weeks in rabbits. The in-vivo degradation of the microspheres was studied microscopically and compared to the in-vitro degradation. The in-vitro and invivo studies showed the biocompatibility of the microspheres of both the hydrophobic and the hydrophilic PEGT/PBT copolymer. Extracts of these microspheres showed no cytotoxic reactivity in the in-vitro cytotoxicity test. Sterilization of the microspheres by gamma irradiation did not affect the cytotoxicity. PEGT/PBT microspheres injected subcutaneously and intramuscularly in rabbits showed a mild tissue response in vivo, in terms of the inflammatory response, the foreign body reaction and the granulation tissue response. Although an in-vitro degradation experiment showed a decrease in molecular weight due to hydrolysis, the in-vivo degradation of the microspheres was slower than previously published.