Reversion of multidrug resistance by co-encapsulation of vincristine and verapamil in PLGA nanoparticles
Reversion of multidrug resistance by co-encapsulation of vincristine and verapamil in PLGA nanoparticles
复制标题
通过将长春新碱和维拉帕米共封装在 PLGA 纳米颗粒中逆转多药耐药性。
DOI：
10.1016/j.ejps.2009.02.018
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发表时间：
2009-06-28
影响因子：
4.6
通讯作者：
Wei, Yu Quan
中科院分区：
文献类型：
--
作者：
Song, Xiang Rong;Cai, Zheng;Wei, Yu Quan
多药耐药(MDR)癌症可以使用包裹的细胞毒药物和化疗增敏剂的组合来治疗。为了优化这种组合方法的有效性，采用O/W乳化溶剂蒸发和盐析法相结合的方法制备了能够输送细胞毒性药物长春新碱、化学增敏剂维拉帕米或它们的组合的聚(D，L-丙交酯-乙交酯)(PLGA)纳米粒制剂。此外，这项工作评估了一些系统地给药化疗增敏剂-细胞毒药物组合的方法。结果表明，抗癌药物和化疗增敏剂的给药顺序是获得最大疗效的关键，长春新碱和维拉帕米同时给药可获得最高的逆转效果。此外，PLGA纳米粒(PLGANPs)对长春新碱耐药的MCF-7/ADR细胞表现出中等的多药耐药逆转活性。双剂载药PLGA纳米粒系统的细胞毒性与一种药物/另一种药物载药的PLGANPs以及两个单药载药的PLGANP联合给药的细胞毒性相似，略高于游离长春新碱/维拉帕米的联合给药。抗癌药物与化疗增敏剂共包裹可降低正常组织的药物毒性，减少药物间的相互作用。因此，我们推测同时负载抗癌药物和化疗增敏剂的PLGANPs可能是治疗体内耐药肿瘤最有潜力的制剂。(C)2009爱思唯尔B.V.保留所有权利。
Multidrug resistant (MDR) cancer may be treated using combinations of encapsulated cytotoxic drugs and chemosensitizers. To optimize the effectiveness of this combinational approach, poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles formulations capable of delivering a cytotoxic drug, vincristine, a chemosensitizer, verapamil, or their combination were prepared via combining O/W emulsion solvent evaporation and salting-out method. Moreover, this work evaluated a number of approaches for the administration of chemosensitizer-cytotoxic drug combinations in a systematic fashion. The results showed that the administration sequence of anticancer drug and chemosensitizer was critical for maximal therapeutic efficacy and the simultaneous administration of vincristine and verapamil could achieve the highest reversal efficacy. In addition, PLGA nanoparticles (PLGANPs) showed moderate MDR reversal activity on MCF-7/ADR cells resistant to vincristine. The dual-agent loaded PLGA nanoparticles system resulted in the similar cytotoxicity to one free drug/another agent loaded PLGANPs combination and co-administration of two single-agent loaded PLGANPs, which was slightly higher than that of the free vincristine/verapamil combination. Co-encapsulation of anticancer drug and chemosensitizer might cause lower normal tissue drug toxicity and fewer drug-drug interactions. Therefore, we speculate that PLGANPs simultaneously loaded with anticancer drug and chemosensitizer might be the most potential formulation in the treatment of drug resistant cancers in vivo. (C) 2009 Elsevier B.V. All rights reserved.