School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
Biomaterials. 2014 Feb;35(7):2391-400. doi: 10.1016/j.biomaterials.2013.11.086. Epub 2013 Dec 19.
We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100-120 nm and EE ranged 85-95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 μg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs.
我们报告了一种策略，利用聚（乳酸-共-乙醇酸）纳米粒子（PLGA NPs）共递送多西他赛（DTX）作为模型抗癌药物与维生素 E TPGS。后者在纳米粒子中充当形成孔的试剂，可能导致更小的粒径、更高的药物包封效率和更快的药物释放，并且还充当生物活性试剂，可抑制 P-糖蛋白以克服癌细胞的多药耐药性。通过纳米沉淀法制备载有 0、10、20 和 40%TPGS 的 DTX-PLGA NPs，并对其粒径和粒径分布、表面形态、物理状态和 NPs 中药物的包封效率进行了表征。所有四种 NPs 的粒径均在 100-120nm 范围内，药物载量约为 10%时 EE 在 85-95%范围内。体外评价表明，游离 DTX 和载有 0、10、20%TPGS 的 DTX-PLGA NPs 的 48 h IC50 值分别为 2.619 和 0.474、0.040、0.009μg/mL，这意味着 PLGA NPs 制剂比游离 DTX 有效 5.57 倍，而载有 10 或 20%TPGS 的 DTX-PLGA NPs 比无 TPGS 的 DTX-PLGA NPs 进一步有效 11.85 倍和 52.7 倍（因此，比游离 DTX 有效 66.0 倍和 284 倍）。异种移植肿瘤模型和免疫组织化学染色分析进一步证实了用 PLGA NPs 共递抗癌药物与 TPGS 的策略的优势。
