紫杉醇聚己内酯／泊洛沙姆188共混载药微球及其抗肿瘤活性

Paclitaxel loaded poly（ e-caprolactone ）/poloxamer 188 blend microspheres and in vivo evaluation of its antitumor activity

目的本研究首次尝试利用聚己内酯（PCL）与亲水性添加剂泊洛沙姆188（Pluronic F68，F68）共混物作为载体材料与抗癌药物紫杉醇组成微球缓释载药系统。方法采用乳化，溶剂挥发法制备紫杉醇PCL/F68共混微球；考察紫杉醇PCL／F68共混微球的表面形态、平均粒径、包埋率及体外释放性能：利用DSC法分析紫杉醇在PCL／F68共混徽球中的分散状态；考察紫杉醇PCL/F68共混微球在小鼠肝癌H22腹水瘤模型中的抗肿瘤活性。结果表明载体材料中的亲水性添加剂F68可在微球表面形成孔状结构，F68的加入提高了紫杉醇从PCL／F68共混载药微球的释放并获得了接近恒定的释放性能；在小鼠肝癌H22腹水瘤模型中。紫杉醇PCL／F68共混载药微球对肿瘤生长具有抑制作用，荷瘤小鼠生存期明显延长。结论以PCL/F68共混物为载体制备的紫杉醇控释微球具有较高的释放能力和明显的控释效果．

Objective To prepare paclitaxel-loaded poly（e-caprolactone）（PCL）/pluronic F68（F68） blend micruspheres as a controlled release system. Methods Paclitaxel-loaded PCL/F68 blend microspheres were prepared by the oil-in water（O/W）emulsion/solvent evaporation method. Characterization of the microspheres followed to examine the particle size, the drug encapsulation efficiency, the surface morphology, in vitro release behavior and DSC analysis. In vivo antitumor activity of paclitaxel-loaded PCL/F68 blend microspheres was evaluated in mice bearing with hepatoma H22 cells ascites tumor. Results The results showed that the porous structure can be formed in the surface of PCL/F68 blend microspheres. Faster and controlled release of paclitaxel from PCIJF68 blend microspheres was achieved in comparison with the PCL microspheres. In animal tests, paclitaxel-loaded PCL/F68 blend mierospheres showed the potent antitumor activity against hepatoma H22 cells in ascites tumor model. Conclusion The paclitaxel loaded PCL/F68 blend microspheres were found to own a faster release rate and a remarkably controlled release behavior.