文献类型：期刊文献

英文题名：Pluronic-based functional polymeric mixed micelles for co-delivery of doxorubicin and paclitaxel to multidrug resistant tumor

作者：Chen, Yanzuo[1,2,3];Zhang, Wei[2,3,4];Huang, Yukun[1];Gao, Feng[1];Sha, Xianyi[2,3];Fang, Xiaoling[2,3]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[2]Fudan Univ, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China;[3]Fudan Univ, Sch Pharm, PLA, Shanghai 201203, Peoples R China;[4]Eastern Virginia Med Sch, Dept Obstet & Gynecol, CONRAD, Arlington, VA 22209 USA

年份：2015

卷号：488

期号：1-2

起止页码：44

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000355887100006)】；

基金：This work was supported by National Natural Science Foundation of China (30901862), Postdoctoral Science Foundation of China (2014M550222), Shanghai Postdoctoral Sustentation Fund (14R21410500) and National Basic Research Program of China (2013CB932500). The authors also acknowledge the support from School of Pharmacy, Fudan University & the Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education (SDD2014-2), and State Key Laboratory of Molecular Engineering of Polymers (Fudan University) (K2015-15).

语种：英文

外文关键词：Doxorubicin; Paclitaxel; Codelivery; Polymeric micelle; Anti-cancer efficacy; Multidrug resistance

摘要：Although doxorubicin (DOX) and paclitaxel (PTX) are widely used in clinic as chemotherapeutics, both drug substances are found to be glycoprotein P (P-gp) substrates which are liable to develop the multidrug resistance (MDR). Additionally, the use of single chemotherapeutic drug has known limitations such as high toxicity profile due to the relatively high doses and limited regimen of clinical application. To this end, Pluronic P105-DOX conjugate was successfully designed and developed which can be further used as a hydrophobic core to entrap another anti-cancer drug PTX with Pluronic F127 to form the dual drug-loaded mixed micelles (PF-DP) in our study, which would offer great advantages over conventional micelles, including easy fabrication, high loading capacity, and co-delivery of hydrophilic DOX and hydrophobic PTX to achieve synergistic effect of these two drug substances. Results showed that. PF-DP possessed a good polydispersity and sustained release profile for both DOX and PTX in vitro. Studies on cellular uptake demonstrated both anti-cancer drugs in PF-DP can effectively accumulate in MDR cancer cells. Furthermore, in vitro cytotoxicity, cell apoptosis and cell cycle arrest studies indicated that PF-DP had better antitumor efficacy in MDR cancer cells compared to those of single-drug loaded micelles. It was also found that PF-DP can suppress the growth of tumor cells more efficiently than single drug formulations at the equivalent drug concentrations, suggesting synergistic effect could be achieved. More importantly, a much stronger antitumor efficacy in MCF-7/ADR tumor-bearing mice was observed in PF-DP group than that of combined administration of free DOX and PTX. Collectively, the dual drug-loaded Pluronic-based functional mixed micelles developed in this study might be a potential nano-drug delivery system for MDR cancer chemotherapy. (C) 2015 Elsevier B.V. All rights reserved.