The Preparation Of Drug-loaded Poly(Propylene Carbonate)S And The Study On Their Biodegradabilities

There is a world-wide research effort to the development of polymeric controlled release drug delivery systems (DDS) for minimizing side effects and toxicity, improving stability and efficacy of drugs is an important issue in pharmacology, biomaterials and clinical medicine fields. The traditional method for preparing DDS through adsorption, embedding and other physical methods to mixing polymer carrier and drugs, can not control the drug encapsulation efficiency, loading capacity and released rate. If the drugs are chemically conjugated by hydrogen or coordination bond, the drug-encapsulation efficiency, drug-loading efficiency and drug-release rate probably becomes more controllable. Aliphatic polycarbonate (APC) possessing good mechanical property, biodegradability, and biocompatibility. The polymers were synthesized by the copolymerization of the corresponding alkyl epoxides and carbon dioxide (CO2), The present thesis focuses on the preparation of drug-loaded APC by "immortal polymerization", and then further studies the degradability of the resultant APC.(1) The preparation and characterization of drug-loaded APC polymer. The binary catalyst system including SalenCo(Ⅲ) Complex and quaternary ammonium salt is a highly selective, and active catalyst for the copolymerization of CO2 and propylene oxide in the presence of ibuprofen at mild conditions. We obtained a serious of ibuprofen-loaded poly(propylene carbonate)s (IBU-PPC) with narrow molecular weight distributions (PDI at around 1.05).(2) The study on IBU-PPC nanoparticles degradability and drug release performance. The drug release of the drug-loaded nanoparticles obtained by the nanoprecipitation exhibits very strong basicity-dependent in basic buffer solution. With the increasing of the basicity, the release rate of ibuprofen becomes fast. The rate gradually decreased due to the consumption of OH’, it was founded that the polymer molecular weight have little effect on release rate of drug.(3) Study on mechanisms of polymer degradation and erosion. Degradation of the polymer chain is an "unzipping" reaction. The reaction was initiated by the deprotonation of-OH end group of IBU-PPC by OH-, then a backbiting fashion leading to the formation of cyclic carbonate. Cyclic carbonate was unstable under alkaline conditions and degraded to CO2 and glycol. This pathway leads to a steady decrease in the polymer molecular weight while maintaining its narrow molecular weight distribution. The IBU-PPC microspheres were biodegraded by clean surface erosion in basic solution. The biodegradation proceeds exclusively at the surface. A fast onset of mass loss could be observed and the molecular weight and molecular weight distribution of the residual mass remains constant until complete disappearance of the implant. The mechanisms of polymer degradation and nanoparticles erosion show good consistency.