A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-beta(25-35)-treated rats following intranasal administration

	A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-beta(25-35)-treated rats following intranasal administration
	Wu HB 1,3; Li JX 2; Zhang QZ 1; Yan XL 1; Guo LR 1; Gao XL 4; Qiu MF 3; Jiang XG*1; Lai R 2; Chen HZ 4; xgjiang@shmu.edu.cn
	2012
发表期刊	EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷号	80 期号:2 页码:368-378
合作性质	其它
摘要	Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs, The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to-brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins
关键词	Odorranalectin Cubosomes Ntranasal Administration Gly14-humanin Brain Delivery Alzheimer's Disease
资助者	Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged.
收录类别	SCI
语种	英语
资助者	Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged. ; Financial support from the National Basic Re- search Program of China (973 Program) 2007CB935800 and 2010CB529806, National Science and Technology Major Project 2009ZX09310-006 and the National Natural Science Foundation of China (No. 30801439) is gratefully acknowledged.
WOS记录号	WOS:000301406600016
引用统计	被引频次：43[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/6923
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
通讯作者	xgjiang@shmu.edu.cn
作者单位	1.School of Pharmacy, Fudan University, Shanghai, China 2.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 3.School of Pharmacy, Shanghai Jiaotong University, Shanghai, China 4.Department of Pharmacology, Shanghai Jiaotong University School of Medicine, Shanghai, China
推荐引用方式 GB/T 7714	Wu HB,Li JX,Zhang QZ,et al. A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-beta(25-35)-treated rats following intranasal administration[J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,2012,80(2):368-378.
APA	Wu HB.,Li JX.,Zhang QZ.,Yan XL.,Guo LR.,...&xgjiang@shmu.edu.cn.(2012).A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-beta(25-35)-treated rats following intranasal administration.EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,80(2),368-378.
MLA	Wu HB,et al."A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-beta(25-35)-treated rats following intranasal administration".EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 80.2(2012):368-378.

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