Paclitaxel nanocrystals for overcoming multidrug resistance in cancer.
Paclitaxel nanocrystals for overcoming multidrug resistance in cancer.
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DOI：
10.1021/mp100012s
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发表时间：
2010-06-07
影响因子：
4.9
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Liu Y;Huang L;Liu F
在这里，我们描述了一种紫杉醇（PTX）纳米晶体制剂，使用D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）作为克服多药耐药性（MDR）的唯一赋形剂，这是当前癌症治疗的一个关键挑战。据我们所知，这是第一次报道PTX纳米晶体可以逆转MDR。TPGS用作表面活性剂以稳定纳米晶体和P-gp抑制剂以逆转MDR。通过透射电子显微镜研究了纳米晶体的尺寸和形貌，并通过粉末X射线衍射确定了晶体结构。体外药物释放曲线显示，与临床紫杉醇制剂紫杉醇相比，纳米晶体表现出缓释动力学。还研究了异种移植模型中的细胞毒性和抗肿瘤功效。紫杉醇/TPGS纳米晶在体内外对紫杉醇耐药的肿瘤细胞有较好的治疗效果，细胞凋亡实验也证实了这一点。我们设想，这种类型的纳米晶体的进一步发展将提供一种新的策略，药物输送和多药耐药治疗。
Here we described a paclitaxel (PTX) nanocrystals formulation using D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as the sole excipient for overcoming multidrug resistance (MDR), a key challenge in current cancer therapy. To the best of our knowledge, it is the first report on PTX nanocrystals which can reverse MDR. TPGS serves as a surfactant to stabilize the nanocrystals and a P-gp inhibitor to reverse MDR. The size and morphology of the nanocrystals were studied by transmission electron microscopy and the crystalline structure was determined by powder X-ray diffraction. In vitro drug release profile showed that the nanocrystals exhibited sustained release kinetics compared to Taxol which is the clinical paclitaxel formulation. The cytotoxicity and antitumor efficacy in xenograft models were also investigated. It is demonstrated that PTX/TPGS nanocrystals have significant advantages over Taxol in achieving better therapeutic effect in Taxol-resistant cancer cells both in vitro and in vivo, which was also confirmed by apoptosis assays. We envision that further development of this type of nanocrystals will provide a novel strategy for drug delivery and multidrug resistance treatment.
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影响因子：
64.8
作者：
SCHIFF, PB;FANT, J;HORWITZ, SB
通讯作者：
HORWITZ, SB
影响因子：
8.8
作者：
Woodcock, D M;Linsenmeyer, M E;Chojnowski, G;Kriegler, A B;Nink, V;Webster, L K;Sawyer, W H
通讯作者：
Sawyer, W H
影响因子：
4.9
作者：
Xu P;Gullotti E;Tong L;Highley CB;Errabelli DR;Hasan T;Cheng JX;Kohane DS;Yeo Y
通讯作者：
Yeo Y
影响因子：
3.7
作者：
Dintaman, JM;Silverman, JA
通讯作者：
Silverman, JA
影响因子：
3.8
作者：
Liu, Feng;Park, Ji-Young;Huang, Leaf
通讯作者：
Huang, Leaf