紫杉醇mPEG-PLA共聚物胶束制备及体外性能

发布时间：2018-11-01 12:51

【摘要】：目的:以甲氧基聚乙二醇-聚乳酸(m PEG-PLA)为载体,研制紫杉醇共聚物胶束(PM-PTX),并评估其体外性能。方法:采用薄膜水化法制备,对PM-PTX的理化性质进行表征,检测药物的体外释放,MTT法考察PM-PTX对Hep-2细胞株的体外细胞毒性。结果:制得的PM-PTX溶液无色透明,透射电镜观察胶束呈类圆形,胶束的包封率为(83.04±1.96)%,载药量为(15.01±0.28)%,平均粒径为(87.74±2.3)nm,多分散指数(PDI)为(0.259±0.014),Zeta电位为(-1.22±0.133)m V,CMC值为0.158 mg·L-1。在3种p H值(5.8,7.2和7.4)环境下,96 h药物的累积释放率分别为(92.19±3.17)%,(88.37±5.62)%和(86.04±2.16)%,无明显差异(P0.05)。与紫杉醇针剂相比,PM-PTX对Hep-2细胞株的体外细胞毒性相对较弱,但胶束组细胞毒性的剂量和时间依赖性更明显。结论:PM-PTX粒径满足淋巴靶向要求,具备缓释性,剂型的改变有利于提高药物抗癌活性。该新剂型对于恶性肿瘤的淋巴化疗具有应用前景。
[Abstract]:Aim: to prepare paclitaxel copolymer micelle (PM-PTX) with methoxy polyethylene glycol (m PEG-PLA) as carrier and evaluate its performance in vitro. Methods: the physicochemical properties of PM-PTX were characterized by membrane hydration method, and the drug release in vitro was detected. The cytotoxicity of PM-PTX to Hep-2 cell line was investigated by MTT method. Results: the PM-PTX solution was colorless and transparent. The micelles were round by transmission electron microscope. The encapsulation efficiency was (83.04 卤1.96)%, the drug loading was (15.01 卤0.28)%, and the average particle size was (87.74 卤2.3) nm,. The polydispersity index (PDI) was (0.259 卤0.014), Zeta potential (-1.22 卤0.133) MV, the CMC value was 0.158 mg L ~ (-1). The cumulative release rates at 96 h were (92.19 卤3.17)%, (88.37 卤5.62)% and (86.04 卤2.16)% under three pH values (5.87.2and 7.4), respectively (P0.05). Compared with paclitaxel injection, the cytotoxicity of PM-PTX to Hep-2 cell line was relatively weak in vitro, but the dose and time dependence of the cytotoxicity of micelle group was more obvious than that of paclitaxel injection. Conclusion: the particle size of PM-PTX can meet the requirement of lymphoid target, and it has the ability to release slowly. The change of dosage form is helpful to improve the anticancer activity of the drug. The new formulation has a promising application in lymphatic chemotherapy of malignant tumors.
【作者单位】：复旦大学附属眼耳鼻喉科医院上海市头颈外科重点学科;复旦大学药学院药剂学教研室;
【基金】：上海市卫生计生委委级科研项目(20124038)
【分类号】：R943

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