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学科主题: 药学
题名:
TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy
作者: Zhang, Jinming1; Li, Yingbo1,2; Fang, Xiefan3; Zhou, Demin2; Wang, Yitao1; Chen, Meiwan1
关键词: Mixed micelles ; Tanshinone IIA ; Apoptosis ; Cancer therapy ; TPGS ; Pluronic F68
刊名: INTERNATIONAL JOURNAL OF PHARMACEUTICS
发表日期: 2014-12-10
DOI: 10.1016/j.ijpharm.2014.09.017
卷: 476, 期:1-2, 页:185-198
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: SALVIA-MILTIORRHIZA BUNGE ; PLURONIC BLOCK-COPOLYMERS ; CONTROLLED DRUG-DELIVERY ; P-GLYCOPROTEIN ; IN-VITRO ; HEPATOMA-CELLS ; APOPTOSIS ; RELEASE ; NANOCARRIERS ; SUCCINATE
英文摘要:

Tanshinone IIA (TAN) has few clinical applications for anti-cancer therapy mainly due to its high lipophicity, low cellular uptake, and poor bioavailability. To improve the anti-cancer effect and bioavailability of TAN, we developed a mixed micelle system constituted with D-alpha-tocopheryl polyethylene glycol succinate-graft-poly(D, L-lactide-co-glycolide) (TPGS-g-PLGA) copolymer and Pluronic F68. TAN was encapsulated in the TPGS-g-PLGA/Pluronic F68 mixed micelles by using the thin film hydration technology optimized by the central composite design/response surface method (CCD/RSM). TAN-loaded mixed micelles were highly stable in the presence or absence of bovine serum albumin (BSA) and achieved sustained drug release in vitro. Compared with free TAN, TAN mixed micelles had higher cytotoxicity and pro-apoptotic effects against human hepatocellular carcinoma HepG2 cells. The significant enhancement on pro-apoptosis by TAN micelles was evidenced by increased chromosome condensation, mitochondria membrane potential loss, cell apoptosis, and cleavages of caspase-3 and PARP. Furthermore, pharmacokinetic studies revealed that TAN mixed micelles significantly prolonged the circulation time and improved bioavailability of TAN in rats. These results demonstrated that TAN-loaded TPGS-g-PLGA/F68 mixed micelles are an effective strategy to deliver TAN for cancer therapy. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 077/2011/A3 ; 062/2013/A2 ; MYRG2014-00033-ICMS-QRCM ; MYRG 208 (Y3-L4)-ICMS11-WYT ; MRG012/WYT/2013/ICMS ; MRG004/CMW/2014/ICMS ; K20130213
项目资助者: Macao Science and Technology Development Fund ; Research Fund of the University of Macau ; State Key Laboratory of Natural and Biomimetic Drugs
WOS记录号: WOS:000345299600025
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59573
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Univ Florida, Coll Med, Dept Pediat, Gainesville, FL 32610 USA

Recommended Citation:
Zhang, Jinming,Li, Yingbo,Fang, Xiefan,et al. TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2014,476(1-2):185-198.
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