芳香开窍中药促进纳米粒经鼻入脑转运及其机制研究

项目名称： 芳香开窍中药促进纳米粒经鼻入脑转运及其机制研究

项目编号： No.81202924

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 胡凯莉

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 药物的脑靶向技术是目前药剂学研究的热点。纳米粒鼻腔给药能以非侵入的方式绕过血脑屏障将多种药物递送入脑，但受到给药量的限制及鼻纤毛清除的影响，其入脑能力仍有待进一步提高。近来研究表明，中药的引经理论与西药的靶向理论有着异曲同工之妙，芳香开窍类脑部引经药可增强多种药物在脑内的浓度，体现靶向作用。因此，我们设想：脑部引经药可以作为一种基于中医引经理论的靶向策略，借助其对鼻粘膜及BBB通透性的调节作用增强纳米粒的经鼻入脑转运。本研究拟通过化学和物理修饰方法制备冰片及β-细辛醚修饰的PLGA纳米粒。以量子点为荧光探针,借助免疫荧光染色、荧光显微及活体成像技术定性定量的探讨引经药修饰促进纳米粒经鼻入脑转运的机制，明确其转运通路，并进行体内外安全性评价。为引经理论与现代靶向策略的结合提供理论基础和实验依据。此外，评价引经药修饰葛根总黄酮脑靶向纳米粒对脑缺血损伤的治疗效果，为该靶向系统的应用提供实验依据。

中文关键词： 芳香开窍中药；鼻腔给药；纳米粒；脑靶向；机理研究

英文摘要： Nowadays, brain drug targeting is the hot spot of pharmaceutical research. Intranasal delivery of nanoparticles can bypass the BBB and delivery various medicines to the brain noninvasively. However, due to the limited administration volume and the clearance action of nasal ciliary, the brain delivery ability of the nanoparticles should be further improved. Recently, the Guiding theory in traditional Chinese medicine was recognized bearing some similarity with the targeting theory. The aromatic refreshing brain guiding medicines can elevate brain concentrations of various medicines showing the targeting effect. Therefore, we suppose, the brain guiding medicines can be a novel targeting strategy based on Guiding theory of traditional Chinese medicine. The effect of brain guiding medicines on regulation of permeability of nasal membrane and the BBB, may enhace the intranasal brain delivery of nanoparticles. In the current project, we will modify PLGA nanoparticles with brain guiding medicines, borneol and β-asarone, by chemical and physical modification methods. Using Qdots as a fluorescent probe, with the add of immunofluorescence staining, fluorescence microscopy and living body imaging techniques, the mechanism and transport passway of intranasal delivered nanoparticles modified by guiding medicines were explore

英文关键词： aromatic refreshing TCM；intranasal administration；nanoparticles；brain targeting；mechanism study