The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages

doi:10.1016/j.ijpharm.2014.08.045

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	The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages
	Liu, H; Zhang, W; Ma, LN; Fan, LL; Gao, FY; Ni, JM; Wang, R; Ni, JM (reprint author), Lanzhou Univ, Sch Basic Med Sci, Sch Life Sci,Sch Pharm, Key Lab Preclin Study New Drugs Gansu Prov, 222 South Tianshui Rd, Lanzhou 730000, Peoples R China.
刊名	INTERNATIONAL JOURNAL OF PHARMACEUTICS
	2014-12-10
卷号	476 期号:1-2 页码:1-8
关键词	Endomorphin-1 Cell penetrating peptides SynB3 Covalent linkage Brain delivery
ISSN号	0378-5173
DOI	10.1016/j.ijpharm.2014.08.045
文献子类	Article
英文摘要	Endomorphins, although they have high analgesic activity and few undesirable side effects, are not in clinical use because of the blood-brain barrier (BBB). One promising solution is to use cell-penetrating peptides (CPPs). CPPs have the ability to translocate cell membranes and have been successfully applied for delivery of therapeutic molecules across the BBB. However, little is known about the transport efficiency of different conjugation strategies between cargo and CPPs. In this study, endomorphin-1 (EM-1) was conjugated with SynB3, an efficient CPP-carrier, via amide, maleimide and disulfide linkages. The delivery efficiency of three linkers was compared in terms of pharmacodynamics and in vitro metabolic stability. Near-infrared fluorescent and fluorescent microscopy experiments were applied to detect the brain uptake and distribution of CPP delivery qualitatively and quantitatively. After the most successful linkage was screened out, the further mechanisms were discussed. We concluded that compared with the other two linkages, the disulfide bond was the most efficient linkage to deliver EM-1 across the BBB and confirmed that it could be reduced at physiological conditions in the brain and release its active form. These findings indicate that for those who need to release a free drug in the brain and maintain activity, a disulfide bond might be the most efficient linkage across the BBB. (C) 2014 Elsevier B.V. All rights reserved.
学科主题	Pharmacology & Pharmacy
出版地	AMSTERDAM
资助项目	国家自然科学基金项目 ; 国家科技重大专项 ; 长江学者和创新团队发展计划 ; 高等学校博士学科点专项科研基金 ; 中央高校基本科研业务费专项资金
项目编号	National Natural Science Foundation of China [81473095, 81273440, 91213302] ; Key National S&T Program of the Ministry of Science and Technology [2012ZX09504001-003] ; Program for Changjiang Scholars and Innovative Research Team in University [IRT1137] ; Specialized Research Fund for the Doctoral Program of Higher Education [20130211130005] ; Research Funds for the Central Universities [lzujbky-2013-ct06, lzujbky-2014-219]
语种	英语
WOS记录号	WOS:000345299600001
资助机构	NSFC ; MOST ; MOE ; LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/121742]
专题	基础医学院_期刊论文
通讯作者	Ni, JM (reprint author), Lanzhou Univ, Sch Basic Med Sci, Sch Life Sci,Sch Pharm, Key Lab Preclin Study New Drugs Gansu Prov, 222 South Tianshui Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Liu, H,Zhang, W,Ma, LN,et al. The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2014,476(1-2):1-8.
APA	Liu, H.,Zhang, W.,Ma, LN.,Fan, LL.,Gao, FY.,...&Ni, JM .(2014).The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages.INTERNATIONAL JOURNAL OF PHARMACEUTICS,476(1-2),1-8.
MLA	Liu, H,et al."The improved blood-brain barrier permeability of endomorphin-1 using the cell-penetrating peptide synB3 with three different linkages".INTERNATIONAL JOURNAL OF PHARMACEUTICS 476.1-2(2014):1-8.