Preparation and anti-MDR tumors study of folate and TPGS dual-modified DSPE-PEG micelles loaded with docetaxel  

叶酸与TPGS修饰的负载多西他赛的DSPE-PEG胶束的制备和抗耐药肿瘤研究（英文）

作　　者：王爱婷[1] 佟淑文 胡新[1] 齐宪荣[3,1,4] 

机构地区：[1]北京大学医学部药学院药剂学系,北京100191 [2]北京泰德制药股份有限公司,北京100176 [3]北京大学医学部分子药剂学与新释药系统北京市重点实验室,北京100191 [4]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2015年第7期419-426,共8页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81273454 and 81473156);Beijing National Science Foundation(Grant No.7132113);National Key Basic Research Program(Grant No.2013CB932501);Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)

摘　　要：Multidrug resistance （MDR） operated by P-glycoprotein （P-gp） is one of the major causes in the treatment failure of cancers. In this work, docetaxel-loaded mixed micelles comprised of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy （polyethylene-glycol）2000 （DSPE-PEG2000）, D-α-Tocopherylpolyethylene glycol 1000 succinate （TPGSIooo） and DSPE-PEG2000-folate were developed to overcome MDR and reduce the side effect of docetaxel in cancer therapy. The diameters of micelles ranged from 13 to 26 nm and the encapsulation efficiencies were all above 85%. The influences of DSPE-PEG2000 and TPGSIooo ratios on the micellar characteristics and anti-resistant tumors effects were evaluated. Micelles with high TPGS1000 amount showed an increased cellular uptake and stronger cytotoxicity against MDR KBv cells. Moreover, the micelles modified by targeting ligand of folic acid exhibited better antitumor effect on folate receptor over-expressing KBv cells. The study provides a method for overcoming MDR in cancer therapy.由P-糖蛋白引起的多药耐药是肿瘤治疗失败的主要原因之一。本研究制备了以DSPE-PEG2000和TPGS1000为脂材、以叶酸为主动靶向配体的负载多西他赛的胶束,用于克服肿瘤多药耐药并降低毒副作用。本研究评价了不同TPGS1000比例对胶束性质和抗耐药肿瘤能力的影响。制备的胶束粒径在13–26 nm,包封率均大于85%。TPGS1000比例的增加可提高耐药肿瘤细胞对胶束的摄取,也可提高胶束对耐药肿瘤细胞的毒性。此外,对于叶酸受体阳性表达的耐药肿瘤细胞,叶酸修饰的胶束有更强的抗肿瘤效果。研究表明,叶酸与TPGS1000共同修饰的胶束对叶酸受体过表达的耐药性肿瘤有更好的治疗效果。

关 键 词：Micelles Multidrug resistance PREPARATION DSPE-PEG TPGS Folate 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]