A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity.
A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity.
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DOI：
10.1016/j.biomaterials.2016.06.002
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发表时间：
2016-09
期刊：
影响因子：
14
通讯作者：
Kabanov, Alexander V.
中科院分区：
文献类型：
--
作者：
He, Zhijian;Wan, Xiaomeng;Schulz, Anita;Bludau, Herdis;Dobrovolskaia, Marina A.;Stern, Stephan T.;Montgomery, Stephanie A.;Yuan, Hong;Li, Zibo;Alakhova, Dania;Sokolsky, Marina;Darr, David B.;Perou, Charles M.;Jordan, Rainer;Luxenhofer, Robert;Kabanov, Alexander V.
紫杉醇（PTX），商业上最成功的抗癌药物，溶解性差，长期以来一直阻碍着合适制剂的开发。在这里，我们提出了PTX纳米制剂的翻译评价，其特征在于易于制备，50%wt的极高载药量。和PTX溶解度高达45 g/L，优异的储存稳定性和可控的，低于100 nm的尺寸。与临床批准的制剂相比，我们观察到有利的体外和体内安全性特征以及更高的最大耐受剂量。药代动力学分析表明，给予的剂量越高，肿瘤对PTX的暴露越高。因此，我们在原位肿瘤模型中观察到改善的治疗结果，包括特别忠实和侵袭性的“T11”小鼠密蛋白低乳腺癌原位、同基因移植。关于所提出的PTX纳米制剂的有希望的临床前数据表明需要研究新的赋形剂，并且是转化为临床试验的坚实基础。
The poor solubility of paclitaxel (PTX), the commercially most successful anticancer drug, has long been hampering the development of suitable formulations. Here, we present translational evaluation of a nanoformulation of PTX, which is characterized by a facile preparation, extraordinary high drug loading of 50 % wt. and PTX solubility of up to 45 g/L, excellent shelf stability and controllable, sub-100 nm size. We observe favorable in vitro and in vivo safety profiles and a higher maximum tolerated dose compared to clinically approved formulations. Pharmacokinetic analysis reveals that the higher dose administered leads to a higher exposure of the tumor to PTX. As a result, we observed improved therapeutic outcome in orthotopic tumor models including particularly faithful and aggressive “T11” mouse claudin-low breast cancer orthotopic, syngeneic transplants. The promising preclinical data on the presented PTX nanoformulation showcase the need to investigate new excipients and is a robust basis to translate into clinical trials.
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DOI：
10.1016/j.jconrel.2011.04.010
发表时间：
2011-07-15
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Luxenhofer R;Sahay G;Schulz A;Alakhova D;Bronich TK;Jordan R;Kabanov AV
通讯作者：
Kabanov AV
影响因子：
4.6
作者：
Luxenhofer, Robert;Han, Yingchao;Schulz, Anita;Tong, Jing;He, Zhijian;Kabanov, Alexander V.;Jordan, Rainer
通讯作者：
Jordan, Rainer
影响因子：
10.8
作者：
Gaertner, Florian C.;Luxenhofer, Robert;Essler, Markus
通讯作者：
Essler, Markus
影响因子：
8.8
作者：
Leonessa, F;Green, D;Licht, T;Wright, A;WingateLegette, K;Lippman, J;Gottesman, MM;Clarke, R
通讯作者：
Clarke, R
影响因子：
3.4
作者：
Seo, Youngee;Schulz, Anita;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.