多西他赛纳米泡的制备和性质

目的：优化多西他赛（docetaxel，DTX）纳米泡处方和工艺，并考察其性质。方法用Langmuir膜天平筛选成膜材料单甲氧基聚乙二醇-聚（乳酸羟基乙酸）共聚物（mPEG-PLGA）与不同膜稳定剂的最佳比例。以沸点为29.5℃的全氟戊烷为有机相，采用注入法制备mPEG-PLGA包裹DTX的纳米胶束，加入全氟戊烷后可形成纳米乳。考察纳米乳的处方工艺、及其形成纳米泡的条件。采用MTT法考察DTX纳米泡的MCF-7细胞毒性。结果成膜材料最佳比例为mPEG-PLGA∶司盘20=10∶1（摩尔比），形成的膜弹性好，可耐受温度和超声。DTX纳米泡有明显的温度和超声敏感性。随温度升高粒径逐渐增大；温度降低粒径减小。在超声作用下，纳米泡先发生合并，粒径变大，随后略有减小。DTX纳米泡有显著的MCF-7细胞毒作用，呈剂量依赖性。结论 DTX纳米泡有望成为肿瘤靶向超声触发释药新制剂。

Preparation and properties of docetaxel-loaded nanobubbles

Objective To optimize the formulation and preparation technology of docetaxel(DTX)-loaded nanobubbles,and evaluate their properties. Methods The best ratio of methoxypoly(ethylene glycol)-poly(DL-lactide-co-glycolide)(mPEG-PLGA) and different membrane stabilizers were optimized with Langmuir membrane balance. DTX-Loaded nano-micelles were encapsulated by mPEG-PLGA with an injection method. Nanoemulsions was formed after being added with perfluoropentane(PFP,the boiling point of 29.5℃)as the organic phase. The formulations and preparation techniques of nanoemulsions were optimized and the conditions of nanobubbles formulaion was also evaluated. Cytotoxicity of DTX-loaded nanobubbles on MCF-7 cells was evaluated with the MTT meth?od. Results The best ratio of mPEG-PLGA and Span 20 was 10∶1(mol/mol). The membrane elasticity of the prepared nanobubbles with optimized formulations and the preparation techniques was good. In addition,they were obviously temperature-sensitive and ultra?sonic-sensitive. The particle size of nanobubbles increased with higher temperature and decreased with lower temperature. The size of nanobubbles increased upon ultrasound application and then decreased a little. The cytotoxicity of DTX-loaded nanobubbles on MCF-7 cells was obvious and dose-dependent. Conclusion DTX-Loaded nanobubbles are a novel formulation with tumor-targeted and ultra?sound-sensitive drug release.