标题:Self-assembled micelles based on Chondroitin sulfate/poly (D,L-lactideco-glycolide) block copolymers for doxorubicin delivery
作者:Zhang, Hui; Xu, Jiangkang; Xing, Liang; Ji, Jianbo; Yu, Aihua; Zhai, Guangxi
作者机构:[Zhang, Hui; Xu, Jiangkang; Xing, Liang; Ji, Jianbo; Yu, Aihua; Zhai, Guangxi] Shandong Univ, Coll Pharm, Dept Pharmaceut, 44 Wenhua Xilu, Jinan 25001 更多
通讯作者:Zhai, Guangxi
通讯作者地址:[Zhai, GX]Shandong Univ, Coll Pharm, Dept Pharmaceut, 44 Wenhua Xilu, Jinan 250012, Peoples R China.
来源:JOURNAL OF COLLOID AND INTERFACE SCIENCE
出版年:2017
卷:492
页码:101-111
DOI:10.1016/j.jcis.2016.12.046
关键词:Block copolymer; Micelles; Chondroitin sulfate; PLGA; DOX
摘要:Doxorubicin (DOX) is one of the most common chemotherapeutic agents for the treatment of various cancers, but its clinical usage is limited by dose-dependent cardiotoxicity. We have recently synthesized a series of Chondroitin sulfate/poly ((D),(L)-lactideco-glycolide) block copolymers (Chs-b-PLGA) with different length of hydrophobic block by an end-to-end coupling strategy. The structure of the amphiphilic block copolymers with low critical micelle concentration (similar to 28 mg/L) were confirmed by H-1 NMR. The copolymers could self-assemble into stable micelles in aqueous environment with homogeneous size distribution and negative zeta potential. The hemolytic study indicated their excellent blood compatibility and potential application for intravenous administration. DOX can be efficiently encapsulated by the Chs-b-PLGA micelles. The DOX-loaded micelles showed a sustained and pH dependent drug release behavior. The cytotoxicity assay showed no associated toxicity with blank micelles while concentration-related cell inhibition with DOX-loaded micelles. Moreover, fast cellular uptake of DOX-loaded micelles was observed by fluorescent microscope. In vivo pharmacokinetics study showed that the Chs-b-PLGA micelles could significantly prolong the blood circulation time of DOX. The maximum tolerated dose (MTD) of DOX-loaded micelles in Kunming mice was about 2-fold higher of the MTD of free DOX, indicating a high tolerance of the DOX-loaded micelles. In conclusion, the Chs-b-PLGA micelles would be a potentially useful drug delivery system for cancer therapy. (C) 2016 Elsevier Inc. All rights reserved.
收录类别:EI;SCOPUS;SCIE
WOS核心被引频次:7
Scopus被引频次:6
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85008675906&doi=10.1016%2fj.jcis.2016.12.046&partnerID=40&md5=91dfdfadb483bab9edb97e58fd92eb3b
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