Preparation and characterization of biodegradable lactic/glycolic acid oligomeric/polymeric microparticulate systems and their application for controlled delivery of active agents.

摘要

Novel injectable, biodegradable composite microsphere drug delivery systems have been developed for long-term protein/peptide drug delivery. These composite microsphere drug delivery systems are based on biocompatible, biodegradable, and bioabsorbable lactic/glycolic acid polymers and natural/synthetic hydrogels.; The whole dissertation is divided into four parts. The first part focuses on the study of the microsphere-forming material, lactic/glycolic acid polymers, used for formulating the systems. In this part of the research, the lactic/glycolic acid polymers with various compositions and molecular weights were synthesized and carefully characterized regarding their identification, composition, molecular weight, crystallinity, viscosity, T_g and T_m. The method for the accurate control of molecular weight by molecular weight moderator was studied. The relationship between polymer molecular weight and the amount of molecular weight moderator was established.; The second part of the research focuses on the biodegradation of the synthesized lactic/glycolic acid polymers and drug delivery application of these polymers for conventional drugs, i.e., aspirin and progesterone. The influences of polymer composition and molecular weight on the polymer degradation were studied. The factors affecting the drug release from the drug delivery systems based on the lactic/glycolic acid polymers were also studied.; The third part of the research focuses on the formulation of nanoparticulate, hydrogel-based drug delivery systems for protein drugs. Three nanoparticulate drug delivery systems based on gelatin, agarose, and poly(vinyl alcohol) (PVA) were prepared and their morphology, size and size distribution, drug loading efficiency, in vitro drug release and protein stability were characterized. This part of the work paved the groundwork for stabilizing protein drugs in microspherical drug delivery systems based on the lactic/glycolic acid polymers.; The final part of this dissertation focuses on the formulation of novel composite microsphere drug delivery systems based on the lactic/glycolic acid polymeric microspheres and hydrogel nanoparticles for protein drug delivery. By introducing hydrogel nanoparticles into the lactic/glycolic acid polymeric microspheres, the new composite microsphere drug delivery systems promoted the advantages and eliminated the drawbacks of both hydrogel nanoparticulate and conventional microsphere systems for controlled-release protein drug delivery. The novel composite microsphere drug delivery systems were characterized with respect to morphology, size and size distribution, drug loading efficiency, in vitro drug release and protein stability.; The novel composite microsphere drug delivery systems are useful for long-term protein/peptide drug delivery. The idea of the novel composite microsphere drug delivery systems can also be applied to other protein/peptide delivery systems to solve the protein instability problems and formulate long-term drug delivery devices.