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目的考察处方和制备工艺对人重组骨形成蛋白-2(rhBMP-2)微球释放度的影响,并比较rhBMP-2微球和rhBMP-2微球温敏性凝胶复合系统的体外释药特性。方法采用W/O/W型乳化溶剂挥发法以聚乳酸-羟基乙酸共聚物(PLGA)和端羧基聚乳酸-羟基乙酸共聚物(PLGA-COOH)为材料制备空白微球。通过吸附法制备rhBMP-2载药微球。以单甲基聚乙二醇-羟基乙酸共聚物(MPEG-PLGA)为材料制备凝胶。通过试管倒转法测定凝胶剂和微球凝胶剂的初始胶凝化温度(IGT),采用夹心法酶联免疫吸附法测定释药速度。结果20%的MPEG-PLGA凝胶和微球凝胶剂的IGT均在37℃左右,微球中药物呈现三相释药模式,而微球凝胶剂体外释药曲线符合Higuchi方程。采用PLGA-COOH制备的rhBMP-2微球,其突释明显小于以PLGA为材料制备的微球,增加内水相与油相的体积比、在内水相中加入氯化钠均可以在一定程度上减小突释。结论rhBMP-2微球温敏性凝胶复合系统可以减少药物突释,具有比微球剂更理想的体外释药特性。
OBJECTIVE To investigate the effects of prescription and preparation process on the release of recombinant human bone morphogenetic protein-2 (rhBMP-2) microspheres and to compare the in vitro release of rhBMP-2 microspheres and temperature-sensitive gel composite system of rhBMP-2 microspheres characteristic. Methods Blank microspheres were prepared by W / O / W emulsion solvent evaporation method using PLGA and PLGA-COOH as materials. Preparation of rhBMP-2 drug-loaded microspheres by adsorption method. The gel was prepared from monomethyl polyethylene glycol-co-glycolic acid (MPEG-PLGA). The initial gelatinization temperature (IGT) of gels and microspheres gels was determined by in vitro tube inversion method. The drug release rate was determined by sandwich enzyme-linked immunosorbent assay. Results The IGT of 20% MPEG-PLGA gel and microsphere gel were about 37 ℃. The drug in the microsphere showed three-phase drug release mode. The in vitro drug release curve of microsphere gel matched Higuchi’s equation. Preparation of PLGA-COOH rhBMP-2 microspheres, the burst was significantly less than PLGA prepared microspheres for the material, increasing the volume ratio of the inner aqueous phase and the oil phase, adding sodium chloride in the inner aqueous phase can be a certain To a lesser extent, burst release. Conclusion The temperature-sensitive gel composite system of rhBMP-2 microspheres can reduce the drug burst, and has better in vitro release characteristics than microspheres.