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Improving the anti-ovarian cancer activity of docetaxel with biodegradable self-assembly micelles through various evaluations.

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机构: [1]Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China [2]Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China [3]Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China
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关键词: MPEG-PCL Docetaxel Self-assembly Ovarian cancer Cell apoptosis Cell growth

摘要:
Docetaxel (DOC) produces anti-tumor effects by inducing apoptosis and inhibiting cell growth. However, its clinical application is limited by its hydrophobicity and low biocompatibility. Therefore, improving DOC's water solubility, biocompatibility, and anti-tumor effects are important goals that will improve its clinical utility. In this work, DOC and methoxy poly(ethylene glycol) (MPEG)/polycaprolactone (PCL) (MPEG-PCL) showed good compatibility through computer simulations. We prepared DOC-loaded polymeric micelles (DOC/MPEG-PCL micelles) with drug loading of 6.82% and encapsulation efficiency of 98.36%; these were monodispersed and approximately 30 nm in diameter, and released DOC over an extended period in vitro and in vivo. In addition, DOC/MPEG-PCL micelles inhibited cell growth and induced apoptosis more effectively than free DOC in vitro. Furthermore, DOC/MPEG-PCL micelles inhibited ovarian tumor growth more significantly than free DOC. Immunohistochemical analysis indicated that DOC/MPEG-PCL micelles improved DOC's anti-tumor effect by enhancing tumor cell apoptosis and suppressing tumor cell proliferation. Moreover, in bio-imaging analysis, DOC/MPEG-PCL micelles showed a higher concentration and a longer retention time in ovarian tumor tissue than did free DOC, indicating that the DOC/MPEG-PCL micelles delivered more anti-tumor drug to the tumor. Our data suggest that DOC/MPEG-PCL micelles have the potential to be applied clinically in ovarian cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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出版当年[2015]版:
大类 | 1 区 工程技术
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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第一作者机构: [1]Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China [3]Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China
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