In vitro degradation and release profiles of poly-DL-lactide-poly(ethylene glycol) microspheres with entrapped proteins

摘要

Poly-DL-lactide (PLA) and poly-DL-lactide-poly(ethylene glycol) (PELA) were produced by bulk ring-opening polymerization using stannous chloride as initiator. PLA, PELA microspheres, and PELA microspheres containing the outer membrane protein (OMP) of Leptospira interrogans with the size of 1.5-2 mu m were prepared by a solvent evaporation process. In vitro degradation and release tests of PLA, PELA, and OMP-loaded PELA microspheres were performed in pH 7.4 buffer solution at 37 degrees C. Quantitatively, the degree of degradation was monitored by detecting the molecular weight reduction, by evaluating the mass loss and the apparent degradation rate constant, and by determining the intrinsic viscosity and poly(ethylene glycol) content of retrieved polymer, while the release profile was assessed by measuring the amount of protein presented in the release medium at various intervals. Qualitatively, the morphological changes of microspheres were observed with scanning electron micrography. The observed relative rates of mass loss versus molecular weight reduction are consistent with a bulk erosion process rather than surface erosion for PELA microspheres. The introduction of hydrophilic poly(ethylene glycol) domains in copolymer PELA and the presence of OMP within microspheres show critical influences on the degradation profile. The OMP-loaded PELA microspheres present triphasic release profile and a close correlation is observed between the polymer degradation and the OMP release profiles. It is suggested that the polymer degradation rate, protein diffusion coefficient, and the water-swollen structure of microspheres matrix commonly contribute to the OMP release from PELA microspheres. (C) 2000 John Wiley & Sons, Inc. [References: 18]