PEG-farnesyl thiosalicylic acid telodendrimer micelles as an improved formulation for targeted delivery of paclitaxel.
PEG-farnesyl thiosalicylic acid telodendrimer micelles as an improved formulation for targeted delivery of paclitaxel.
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DOI：
10.1021/mp500181x
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发表时间：
2014-08-04
影响因子：
4.9
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Zhang X;Huang Y;Zhao W;Chen Y;Zhang P;Li J;Venkataramanan R;Li S
我们最近设计并开发了一种基于聚乙二醇（PEG）衍生法尼基硫代水杨酸酯（FTS，一种无毒Ras拮抗剂）的双功能药物载体。PEG5K-FTS2很容易形成胶束（20-30 nm），疏水药物如紫杉醇（PTX）可以有效地装载到这些胶束中。在同基因乳腺癌小鼠模型中，PEG5K-FTS2胶束中配制的PTX显示出比紫杉醇更有效的抗肿瘤活性（4T1.2）。为了进一步完善我们的PEG-FTS胶束体系，我们开发了4种PEG-FTS偶联物，它们的分子量（PEG2K vs PEG5K）和共轭物中PEG/FTS的摩尔比（1/2 vs 1/4）不同。对这些偶联物进行了表征，包括CMC、载药能力、稳定性以及它们在体外和体内向肿瘤细胞递送抗癌药物PTX的功效。我们的数据表明，与4个FTS分子的共轭物比与2个FTS分子的共轭物更有效，与PEG5K的共轭物比与PEG2K的共轭物更有效地形成稳定的混合胶束。在PEG5K-FTS4胶束中配制的PTX是体内抑制肿瘤生长最有效的配方。
We have recently designed and developed a dual-functional drug carrier that is based on poly(ethylene glycol) (PEG)-derivatized farnesylthiosalicylate (FTS, a nontoxic Ras antagonist). PEG5K-FTS2 readily form micelles (20–30 nm) and hydrophobic drugs such as paclitaxel (PTX) could be effectively loaded into these micelles. PTX formulated in PEG5K-FTS2 micelles showed an antitumor activity that was more efficacious than Taxol in a syngeneic mouse model of breast cancer (4T1.2). In order to further improve our PEG-FTS micellar system, four PEG-FTS conjugates were developed that vary in the molecular weight of PEG (PEG2K vs PEG5K) and the molar ratio of PEG/FTS (1/2 vs 1/4) in the conjugates. These conjugates were characterized including CMC, drug loading capacity, stability, and their efficacy in delivery of anticancer drug PTX to tumor cells in vitro and in vivo. Our data showed that the conjugates with four FTS molecules were more effective than the conjugates with two molecules of FTS and that FTS conjugates with PEG5K were more effective than the counterparts with PEG2K in forming stable mixed micelles. PTX formulated in PEG5K-FTS4 micelles was the most effective formulation in inhibiting the tumor growth in vivo.
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影响因子：
4.2
作者：
Baines AT;Xu D;Der CJ
通讯作者：
Der CJ
影响因子：
45.3
作者：
WEISS, RB;DONEHOWER, RC;LEYLANDJONES, B
通讯作者：
LEYLANDJONES, B
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
14
作者：
Lu, Jianqin;Huang, Yixian;Zhao, Wenchen;Marquez, Rebecca T.;Meng, Xiaojie;Li, Jiang;Gao, Xiang;Venkataramanan, Raman;Wang, Zhou;Li, Song
通讯作者：
Li, Song
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K