【摘要】 目的制备紫杉醇/聚乙二醇-聚谷氨酸苄酯纳米胶束的冻干粉针剂。方法以胶束粒径、有机溶剂残留量等为评价指标,采用膜透析法制备纳米胶束;以冻干成品的外观形态、体外释药曲线为评价指标,优选冻干粉针剂的制剂处方;研究粉针剂的冻干工艺及该粉针剂对HepG-2肝癌细胞的体外细胞毒性。结果以3%甘露醇为比例,制备获得紫杉醇纳米胶束冻干粉针剂外观良好,其体外释药曲线具有突释与缓释特性,且与新鲜透析所得载药纳米胶束溶液的释药曲线基本相同;当紫杉醇浓度≤10μg·mL-1时,冻干粉针剂对HepG-2肝癌细胞的细胞毒性远低于市售紫杉醇注射剂(P<0.01)。结论采用膜透析结合冷冻干燥法制备紫杉醇纳米胶束冻干粉针剂,避免使用紫杉醇增溶剂(聚氧乙烯蓖麻油)带来的不良过敏反应,并降低对体外肝癌细胞的细胞毒性,具有较好的临床价值与应用前景。更多还原

【Abstract】 Objective To prepare the paclitaxel- loaded polyethylene glycol- polybenzyl- L- glutamate(PEG- PBLG)lyophilized nano- micelles and to study the in vitro properties of the nano- micelles. Methods With the micelle particle diameter and organic solvent residual volume as the evaluation indexes, paclitaxel- loaded lyophilized nano- micelles with amphiphilic copolymer PEG- PBLG was prepared by the membrane dialysis method. The preparation formula of paclitaxel- loaded lyophilized nano- micelles was optimized with the lyophilized nano- micelles macroscopic appearance and in-vitro drug- release curve as the indexes. The in vitro effects of paclitaxel- loaded lyophilized nano- micelles and commercially available paclitaxel injection with Cremophor EL on the growth of tumor cells were observed. Results The paclitaxel- loaded lyophilized nano- micelles showed better macroscopic appearance when the proportion of manicol was 3 %. The in vitro paclitaxel release profile was characterized with a rapid release at the initial stage and then following by smooth and sustained- release from the lyophilized nano- micelles. At low concentration of paclitaxe(l≤10μg·mL-1), the paclitaxel- loaded PEG- PBLG lyophilized nano- micelles displayed much less cell cytotoxicity than paclitaxel injection with Cremophor EL(P < 0.01). Conclusion The paclitaxel- loaded PEG- PBLG lyophilized nano- micelles have less cytotoxicity than the commercially available paclitaxel injections with Cremophor EL. Hence,paclitaxel- loaded PEG- PBLG micelles would be a novel paclitaxel preparation in clinic for the treatment of tumor.更多还原