Synthesis Of Stellate Polylactic Acid - Glycolic Acid Copolymer And Study On Sustained Release Microspheres

In this paper, stellate polylactic-co-glycolic acid (star-PLGA) was synthesized by D, L-lactide, glycolide and glucose through ring-opening polymerization reaction. The star-PLGA was characterized by infrared spectroscopy (IR), hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and glucose response.Mabuterol hydrochloride and gastrodin were selected as model drugs and star-PLGA were used as carriers to prepare biodegradable and biocompatible microspheres (MS) for evaluating the performance of star-PLGA. Furthermore, the formulas and conditions of preparation, the drug release in vitro of microspheres were also studied.High-performance liquid chromatography (HPLC) method with UV detector were applied to detect drugs release in vitro, respectively. Analysis methods above were proved to be sensitive, stable, precise and reliable.Mabuterol hydrochloride-MS and gastrodin-MS with star-PLGA as carriers were prepared by double emulsification-solvent evaporation method, respectively. The influence of formulation and manufacture was studied with drug loading, burst effect and particle size as evaluating criterias. Based on the results of single factor experiments, the formulations were optimized by orthogonal design.The characteristics of mabuterol hydrochloride-MS prepared with optimal formulation were investigated and evaluated. The results showed that mabuterol hydrochloride-MS had good appearance with drug loading of 1.59%and burst effect of 5.15%. Results of the influence tests indicated that mabuterol hydrochloride-MS was unstable under the condition of high temperature, high humidity and illumination. Results of the long-term test indicated that mabuterol hydrochloride-MS was stable under the condition of room temperature in 2 months.The characteristics of gastrodin-MS prepared with optimal formulation were investigated and evaluated. The results showed that gastrodin-MS had good appearance with drug loading of 5.28%and burst effect of 15.06%. Results of the influence tests indicated that gastrodin-MS was unstable under the condition of high temperature, high humidity and illumination. Results of the long-term test indicated that gastrodin-MS was stable under the condition of room temperature in 1 month. The gastrodin-MS was intramuscular administrated to wistar rats. The drug release profile in vivo was evaluated. A reliable analysis method by HPLC was established to determine the surplus amount of gastrodin in the inject location. The results showed that there was good relationship between the in vivo release and in vitro release experiments.