Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin

doi:10.1016/j.polymer.2010.09.004

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin
	Fan, Honglei 3; Huang, Jin 2,3; Li, Yaping4 ; Yu, Jiahui 2; Chen, Jinghua 1
刊名	POLYMER
	2010-10-15
卷号	51 期号:22 页码:5107-5114
关键词	Reduction-degradable Camptothecin Micelle
ISSN号	0032-3861
DOI	10.1016/j.polymer.2010.09.004
文献子类	Article
英文摘要	This research is aimed to develop a reduction-degradable micelle delivery system based on polymer-camptothecin (CPT) conjugate in order to enhance the solubility and stability of CPT in aqueous media. Firstly, disulfide-linked poly(amido amine) (SS-PAA) containing alkyne groups was synthesized by Michael addition polymerization between propargyl amine and N,N'-bis(acryloyl) cystamine (BAC). And then, azide-functionalized CPT derivatives were conjugated with SS-PAA by click cycloaddition. Further grafting of residual alkyne groups in SS-PAA with azide-terminated poly(ethylene glycol) methyl ether (mPEG) gave mPEG-g-SS-PAA-CPT conjugate. At last, micelles with size of ca. 88 nm were fabricated from mPEG-g-SS-PAA-CPT conjugate, suggesting their passive targeting potential to tumor tissue. It was worthy of note that the drug-loaded system of mPEG-g-SS-PAA-CPT micelles improved the solubility and stability of CPT in aqueous media. Owing to the reduction degradability of disulfide linker in main chain of mPEG-g-SS-PAA-CPT, the CPT sustainably release from micelles together with the gradual cleavage of polymer in the presence of dithiothreitol (OTT) at the concentration of simulating the intracellular condition while almost no change occurred at the level of OTT corresponding to extracellular condition. Furthermore, the cell viability results showed the essential decrease of cytotoxicity to L929 cell line. These results present a strategy in designing anti-tumor CPT-polymer conjugates for highly selective delivery to tumor cells. (C) 2010 Elsevier Ltd. All rights reserved.
资助项目	Chinese Ministry of Science and Technology[2009CB930300] ; National Natural Science Foundation of China[50873080] ; Shanghai Municipality Commission for Special Project of Nanometer Science and Technology[0952nm05300] ; Shanghai Municipality Commission for Non-governmental International[09540709000] ; International Corporation[10410710000] ; Foundation for New Century Excellent Talents in University of Ministry of Education of China[NCET-10-0435] ; Fundamental Research Funds[WUT 2010-II-022] ; Fundamental Research Funds[JUSRT30905]
WOS关键词	TRANSFER RADICAL POLYMERIZATION ; ANTITUMOR-ACTIVITY ; DRUG-DELIVERY ; TOPOISOMERASE-I ; POLYMERS ; RELEASE ; BIODEGRADATION ; DERIVATIVES ; CHEMISTRY ; TOXICITY
WOS研究方向	Polymer Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000283479000015
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278746]
专题	药物制剂研究中心
通讯作者	Huang, Jin
作者单位	1.Jiangnan Univ, Sch Med & Pharmaceut, Wuxi 214122, Peoples R China 2.E China Normal Univ, Inst Adv Interdisciplinary Res, Shanghai 200062, Peoples R China; 3.Wuhan Univ Technol, Coll Chem Engn, Wuhan 430070, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Fan, Honglei,Huang, Jin,Li, Yaping,et al. Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin[J]. POLYMER,2010,51(22):5107-5114.
APA	Fan, Honglei,Huang, Jin,Li, Yaping,Yu, Jiahui,&Chen, Jinghua.(2010).Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin.POLYMER,51(22),5107-5114.
MLA	Fan, Honglei,et al."Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin".POLYMER 51.22(2010):5107-5114.