紫杉醇mPEG-PLA共聚物胶束制备及体外性能  

Preparation and in vitro characterization of paclitaxel-loaded mPEG-PLA polymer micelles

作　　者：高敏琦 任恒磊[1] 谢操[2] 谢明[1] 

机构地区：[1]复旦大学附属眼耳鼻喉科医院上海市头颈外科重点学科,上海200031 [2]复旦大学药学院药剂学教研室,上海201203

出　　处：《中国新药杂志》2017年第16期1948-1953,共6页Chinese Journal of New Drugs

基　　金：上海市卫生计生委委级科研项目(20124038)

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(P>0.05)。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。Objective： To establish a novel colloidal system composed of mPEG-PLA loaded with paclitaxel （PM-PTX） and investigate the in vitro properties. Methods： PM-PTX were prepared by thin-film dispersion method. The micelle properties and in vitro drug release were investigated. The in vitro cytotoxicity of PM-PTX against Hep-2 cancer cells was evaluated by MTT assay. Results： The micelles were spherical in shape and had smooth surface as examined by TEM. The encapsulation efficiency and drug loading were （83.04 ± 1.96） % and （15.01 ±0.28）% , respectively. The average size of the mieelles was （87.74± 2.3 ） nm, with a polydispersity index （PDI） of （0.259 ±0.014）, a zeta potential of （-1.22±0.133） inV. The CMC value for micelles was 0. 158 mg·L^-1. After 96 h, the cumulative amount of released PTX was （92.19 ±3.17）%, （88.37 ±5.62）% and （86.04 ±2. 16）% under pH 5.8, 7.2 and 7.4, respectively. The pH values of the release media did not notably affect the drug release patterns （P 〉 0.05 ）. The PTX injection showed an overall higher cytotoxicity against Hep-2 cells in comparison to PM-PTX. The time- and concentration-dependency of the cytotoxicity of PM-PTX was more obvious compared with PTX injection. Conclusion： The presently developed micelles meet the requirements on particle size for lymphatic uptake. Encapsulation of paclitaxel into sustain-released carriers seems to improve the antitumor efficiency of the drug. PM-PTX might serve as a potential antitumor drug delivery system for the treatment of lymphatic metastases of malignant tumors.

关 键 词：紫杉醇 甲氧基聚乙二醇-聚乳酸 共聚物胶束 体外细胞毒性 

分 类 号：R944[医药卫生—药剂学]