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

文献类型:期刊论文

作者Wu HB1,3; Li JX2; Zhang QZ1; Yan XL1; Guo LR1; Gao XL4; Qiu MF3; Jiang XG[*]1; Lai R2; Chen HZ4
刊名EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
出版日期2012
卷号80期号:2页码:368-378
关键词Odorranalectin Cubosomes ntranasal administration Gly14-Humanin Brain delivery Alzheimer's disease
通讯作者xgjiang@shmu.edu.cn
合作状况其它
英文摘要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
收录类别SCI
资助信息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.
语种英语
WOS记录号WOS:000301406600016
公开日期2012-04-20
源URL[http://159.226.149.42:8088/handle/152453/6923]  
专题昆明动物研究所_动物毒素室
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.,...&Chen HZ.(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.

入库方式: OAI收割

来源:昆明动物研究所

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