载盐霉素聚合物胶束的构建与抗肿瘤干细胞的体外研究  

Preparation of Salinomycin-Loaded Micelles and the Effects on Cancer Stem Cells in Vitro

作　　者：张杨[1] 代文兵[2] 王坚成[2] 张强[2] 

机构地区：[1]首都医科大学附属北京友渲医院药剂科,北京100050 [2]北京大学药学院,天然约物与仿生药物国家重点实验室,北京100191

出　　处：《中国药学杂志》2014年第5期384-391,共8页Chinese Pharmaceutical Journal

摘　　要：目的制备一种包载难溶性药物盐霉素的新型聚合物胶束系统,以提高其水溶性,并对其体外抗肿瘤干细胞作用进行评价。方法以聚乙二醇-聚己内酯嵌段共聚物(mPEG-b-PCL)作为载体材料,将盐霉素物理包载于聚合物胶束的内部,同时对聚合物胶束的制备方法和载药胶束的处方进行了优化,并进一步对最优处方的粒径及分布、形态、稳定性、释药规律等理化性质进行了考察;最后采用侧群细胞(Side Population,SP)分析的方法测定了载药胶束对MCF-7细胞体外活性的影响。结果聚合物胶束的最优处方为药物(SAL)与聚合物材料(mPEG-b-PCL)的质量比1∶20,该体系微粒的粒径小于30 nm,外观呈球形,大小分布均匀;载药胶束溶液的耐稀释性和热稳定性均良好。载盐霉素胶束能够降低MCF-7细胞中SP细胞的比例。结论本实验制备的聚合物胶束载药系统能够显著提高盐霉素的水溶性,并对乳腺癌干细胞表现出了选择性杀伤作用。OBJECTIVE To design and prepare a novel polymeric micelles preparation for hydrophobic salinomycin（SAL） , then evaluate the effects of SAI, micelles on cancer stem cells in vitro. METHODS SAL was entrapped into polymeric micelles constructed from amphiphilic diblock copolymer of poly（ethylene glycol）-block-poly（ε-caprolactone） （mPEG-b-PCL）. Firstly, the process of pre- paring micelles and formulation composition were optimized. Then, the physicochemical properties such as particle size distribution, shape and surface morphology, stability and release rates of SAL-loaded micelles were studied. Finally, the side population（SP） cells were analyzed to evaluate the effects of SAL micelles on the MCF-7 cells. RESULTS The optimal formulation of drug-loaded mieelles was mPEG-b-PCL copolymers and SAL（20： 1, w/w） ; the average particle size of SAL-loaded micelles was less than 30 nm, with nar- row size distribution, unitbrm spherical shape and good stability. In vitro studies denlonstrated that SAL-loaded micelles were able to decrease the proportion of SP cells. CONCLUSION Polymeric micelles are capable of overeoming the poor solubility of SAL, and SAL-loaded micelles can selectively deplete breast cancer stem cells.

关 键 词：盐霉素 胶束 肿瘤干细胞 MCF-7 侧群细胞 

分 类 号：R944[医药卫生—药剂学]