载羟基喜树碱聚乳酸-羟基乙酸微球的制备及相关性能研究

Preparation and characterization of poly(lactic-co-glycolic acid) microspheres containing 10-hydroxycamptothecin

目的制备一种载羟基喜树碱的聚乳酸-羟基乙酸(PLGA)缓释微球,并考察其相关性能。方法采用乳化-溶剂挥发法制备羟基喜树碱PLGA微球,用扫描电子显微镜观察载药微球表面形态,测定平均粒径及跨距,高效液相色谱检测包封率、载药率及体外释放情况,改良寇氏法计算小鼠半数致死量。结果制备的载药PLGA微球呈圆球形,表面光滑,无粘连,平均粒径30.8μm,跨距0.9,包封率为85.5%、载药率4.28%,在体外28 d累积释放药物81.4%。羟基喜树碱小鼠静脉注射的半数致死量为18.4 mg/kg,肌内注射半数致死量为71.3 mg/kg,而羟基喜树碱PLGA微球肌内注射的半数致死量为138.5 mg/kg。结论乳化-溶剂挥发法制备的羟基喜树碱PLGA微球粒径适宜,包封率、载药率高,缓释效果好,毒性低,具有潜在的临床应用价值。

Objective To prepare and characterize the poly（lactic--co-glycolic acid ）（PLGA） microspheres containing 10- hydroxycamptothecin （PMCH）. Methods PMCH were prepared by emulsion-solvent evaporation method, the morphology was examined by scanning electron microscope, the encapsulation efficiency, drug loading rate and in vitro release were measured by high- performance liquid chromatography, and the median lethal dose on mice was calculated by modified Cole＇s method. Results Theprepared PMCH were spherical in shape with a mean size of 30.8 μm, encapsulation efficiency of 85.5 %, drug loading rate of 4.28 %. The cumulative release of hydroxyeamptothecin from microspheres was 81.4 % within 28-day. The median lethal dose of 10- hydroxycamptothecin on mice was 18.4 mg/kg by intravenous injection, 71.3 mg/kg by intramuscular injection, and 138.5 mg/kg whenusing PMCH intramuscular injection. Conclusion It is demonstrated that PLGA microspheres containing lO-hydroxycamptothecin were successfully prepared by emulsion-solvent evaporation method with optimal particle size, high drug loading rate and encapsulation efficiency, suitable release kinetics, and low toxicity, which would possess potential clinical application value.