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TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy
Zhang J.1; Li Y.1,2; Fang X.3; Zhou D.2; Wang Y.1; Chen M.1
2014
Source PublicationInternational Journal of Pharmaceutics
ISSN3785173
Volume476Issue:1Pages:185
Abstract

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-α-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. © 2014 Elsevier B.V. All rights reserved.

KeywordApoptosis Cancer Therapy Mixed Micelles Pluronic F68 Tanshinone Iia Tpgs
DOIhttp://doi.org/10.1016/j.ijpharm.2014.09.017
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000345299600025
The Source to ArticleScopus
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Cited Times [WOS]:40   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang Y.; Chen M.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
2.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3.Department of Pediatrics, College of Medicine, University of FL, Gainesville, FL 32610, USA
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang J.,Li Y.,Fang X.,et al. TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy[J]. International Journal of Pharmaceutics,2014,476(1):185.
APA Zhang J.,Li Y.,Fang X.,Zhou D.,Wang Y.,&Chen M..(2014).TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy.International Journal of Pharmaceutics,476(1),185.
MLA Zhang J.,et al."TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy".International Journal of Pharmaceutics 476.1(2014):185.
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