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首页 » 药物递送 » Eur J Pharm Bio:蒋兴国等小分子凝集素作为药物靶向输送载体研究获进展

Eur J Pharm Bio:蒋兴国等小分子凝集素作为药物靶向输送载体研究获进展

来源:中科院昆明动物研究所 2012-02-15 14:00

凝集素长期以来在药剂学研究上作为重要的靶向输送载体,但绝大部分凝集素分子量较大、可能存在毒性、免疫原性等缺陷限制了其应用。小分子凝集素是优良的药物靶向候选载体分子。中国科学院昆明动物研究所赖仞研究员领导的学科组从两栖动物皮肤中识别了一目前分子量最小的凝集素(1700 Da,PLoS one,2008)。

最近,昆明动物所该研究团队与复旦大学药学院蒋兴国教授领导的课题组合作,利用微球体技术将治疗帕金森氏病的神经保护性肽与该小分子凝集素结合,通过鼻腔给药,在大鼠实验动物模型上研究其靶向输送效率。研究表明,通过该小分子凝集素作为输送载体,可以提高神经保护性肽的治疗效果。该研究提供了一种有效的非损伤性药物分子入脑的药物输送系统。

该研究结果“A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-β(25-35)-treated rats following intranasal administration。”发表于国际杂志Eur J Pharm Biopharm上。

A novel small Odorranalectin-bearing cubosomes: Preparation, brain delivery and pharmacodynamic study on amyloid-β25–35-treated rats following intranasal administration

Hongbing Wua, c, 1, Jianxu Lib, 1, Qizhi Zhanga, Xiluan Yana, Liangran Guoa, Xiaoling Gaod, Mingfeng Qiuc, Xinguo Jianga, , , Ren Laib, Hongzhuan Chend

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.

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