Synergistic co-delivery of doxorubicin and paclitaxel using multi-functional micelles for cancer treatment
Synergistic co-delivery of doxorubicin and paclitaxel using multi-functional micelles for cancer treatment
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DOI：
10.1016/j.ijpharm.2013.06.017
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发表时间：
2013-09-15
影响因子：
5.8
通讯作者：
Yung, Lin-Yue Lanry
中科院分区：
文献类型：
--
作者：
Duong, Hoang Hanh Phuoc;Yung, Lin-Yue Lanry
本研究的主要目的是证明联合阿霉素（D）和紫杉醇（P）的协同抗癌药物系统，通过细胞穿透和细胞靶向部分的帮助，以提高癌症治疗效果。首先，考察了联合游离药物（D/P）的协同作用，以获得适合后续研究的剂量组合。游离药物D/P以1/0.2的摩尔比组合与游离单一药物D或P的处理相比显示协同治疗效果。其次，两种单一载药胶束的持续释放系统，（i）共递送D-FOL胶束和P-FOL胶束系统和（ii）共递送D-TAT/FOL胶束和P-TAT/FOL胶束系统，在DIP摩尔比为1/0.2时，结果显示协同效应，与仅F0 L系统相比，达特/F0 L系统具有更高的功效。最后，设计了一种具有缓释、协同药物相互作用、选择性靶向肿瘤细胞和高细胞穿透能力的双D/P负载系统。D/P-TAT/FOL胶束的IC 50值为0.172 μ M D/0.043 μ M P，远低于未官能化的单一载药胶束的IC 50值（D-胶束为3.873 μ M，P-胶束为0.790 μ M）。总的来说，这种新开发的多功能载体中D和P的双重包封将是一种有前途的癌症治疗技术。(C)2013爱思唯尔有限公司版权所有。
The main purposes of this study are to demonstrate the synergistic anticancer drug systems with the combined doxorubicin (D) and paclitaxel (P) via the aid of cell penetrating and cell targeting moieties for enhancing the cancer therapeutic effect. Firstly, the synergistic effect of combined free drugs (D/P) was investigated to obtain the suitable dose combination for subsequent studies. The combination of free drugs D/P at molar ratio of 1/0.2 shows synergistic therapeutic effect compared with the treatment of a free single drug D or P. Secondly, sustainable release systems of two single drug-loaded micelles, (i) co-delivered D-FOL micelle & P-FOL micelle system and (ii) co-delivered D-TAT/FOL micelle & P-TAT/FOL micelle system, at DIP molar ratio of 1/0.2 were investigated. The results show synergistic effect with the higher efficacy of the TAT/FOL system compared to FOL only system. Finally, a dual D/P-loaded system with sustainable release rate, synergistic drug interaction, selective targeting to cancer cells and high cell penetrating ability was designed. The D/P-TAT/FOL micelles exhibit an IC50 value of 0.172 mu M D/0.043 mu M P, which is much lower than the IC50 values of the single drug-loaded micelles without functionalization (3.873 mu M for D-micelles and 0.790 mu M for P-micelles). Overall, this newly developed dual encapsulation of D and P in the multifunctional carrier would be a promising technology for cancer treatment. (C) 2013 Elsevier B.V. All rights reserved.