白蛋白紫杉醇聚合物胶束抑瘤效果研究

Anti-tumor Effect of Albumin-Paclitaxel Polymeric Micelle

目的研制紫杉醇聚合物胶束(PTX PM)和白蛋白紫杉醇聚合物胶束(HSA-PTX PM)制剂,比较该两组制剂与市售紫杉醇注射液(PTX injection)的抑瘤效果。方法用激光动态光散射粒度仪检测这两组制剂的粒度分布,透射电镜观察粒子形态。采用传统抑瘤率实验方法和活体动物成像技术方法同时评价抑瘤效果。建立荷B16黑色素瘤C57小鼠模型,考察制剂组对小鼠生存期的影响。结果 2种制剂的粒径有效光强粒径均在100 nm左右。透射电镜显示粒子呈圆整的球形。活体成像图片显示PTX PM和HSA-PTX PM制剂的抑瘤效果优于PTX injection,其中HSA-PTX PM的抑瘤效果更佳。HSA-PTX PM的抑瘤率为72.92%,优于PTX PM(66.49%),明显优于PTX injection(47.68%)(P<0.05)。用传统实验方法计算得到的结果基本一致。生存期实验显示,与市售相比HSA-PTX PM更能延长荷瘤小鼠的平均生存期。结论 PTX PM和HSA-PTX PM的抑瘤效果要优于市售紫杉醇注射液,并且HSA-PTX PM更优。聚合物胶束和白蛋白两种载体联用在抗肿瘤药物制剂技术领域有很好的发展前景。

OBJECTIVE To develop paclitaxel polymeric micelle（ PTX PM） and albumin-paclitaxel polymeric micelle（ HSA-PTX PM） ,to evaluate the anti-tumor activity of two formulations and the PTX injection sold in market. METHODS The panicle size and morphology of PTX PM and HSA-PTX PM were analyzed by ZetePALS Zeta Potential Analyzer and Transmission Electron Microscope. The anti-tumor activity was determined by traditional method and in vivo imaging technique method. The effect of two formulations on life span of B16 tumor-bearing mice was investigated by the BI6 tumor-bearing mouse model . RESULTS The size distributions of PTX PM and HSA-PTX PM were similar. The effective diameters of two formulations were both around 100 nm. The appearance of the panicle was spherical. In vivo imaging pictures showed HSA-PTX PM and PTX PM obtained better anti-tumor effect than the PTX in- jection and HSA-PTX PM was best. HSA-PTX PM with the inhibition rate of 72.92% was better than PTX PM （66.49%）and PTX injection（47.68% ） （P 〈0. 05）. The results were similar to the traditional method. HSA-FFX PM prolonged the mean life span of B16 tumor-bearing mouse compared with PTX injection. CONCLUSION The anti-tumor activities of PTX PM and HSA-PTX PM was better than PTX injection while HSA-PTX PM was the best. The technology using the drug carrier albumin together with polymeric micelle has a wonderful prospect.