剪应力响应的二氢杨梅素Pickering乳液用于治疗动脉粥样硬化的研究

项目名称： 剪应力响应的二氢杨梅素Pickering乳液用于治疗动脉粥样硬化的研究

项目编号： No.81503013

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 熊微

作者单位： 华中科技大学

项目金额： 17.9万元

中文摘要： 动脉粥样硬化（AS）是一种严重危害人类健康的慢性疾病，由于缺乏特异性的生物标志物，药物难以靶向至病变部位。AS会导致血管狭窄，剪应力大幅增加，这一独有的病理特征可作为其靶向治疗的突破口。我们研究发现，以纳米凝胶为界面稳定剂的Pickering乳液，其稳定性可通过改变凝胶的两亲性和尺寸而调整，有望作为剪应力响应的药物载体用于AS的靶向治疗。本项目根据前期在纳米凝胶上的基础，以二氢杨梅素（DMY）为治疗药物，构建弱稳定性的Pickering乳液。该乳液能在正常血流中稳定存在，但在AS狭窄处会因剪应力增大而解体释放药物，从而具备AS剪应力响应性。本项目的实施有望获得一种新型的剪应力响应的药物载体，具有AS的靶向性；能消除DMY本身理化性质对药物吸收、分布、跨膜转运等过程的不利影响，发挥DMY多靶点抗AS效果，并对在细胞和分子生物水平上深入了解中药有效成分抗AS作用机制提供一种新的研究思路和方法。

中文关键词： 药物输送；纳米凝胶；Pickering乳液；剪应力响应；动脉粥样硬化

英文摘要： Atherosclerosis (AS) is a chronic disease that endangers the human health seriously. Since no disease-specific biomarker has been identified for atherosclerosis so far, the challenge remains to discover an approach that allows drug targeting to a symptomatic culprit lesion. Stenotic blood vessels caused by AS exhibit unique physical characteristics that distinguish them from normal vasculature in that fluid shear stress can significant increase locally. It may become a breakthrough point of AS targeted therapy. We found the Pickering emulsion that was fabricated with nanogels assembling at O/W interfaces, could adjust its stability by controlling the nanogels' amphipathic properties and particle sizes. It was therefore expected to be a drug carrier that targets drugs to stenotic sites in blood vessels to treat AS. According to the basis of design and preparation of nanogels, the project will choose dihydromyricetin (DMY) as drug and synthesize suitable nanogels to construct Pickering emulsion with weak stability. The Pickering emulsion could stably exist in the normal vasculature, but break and release DMY at stenotic sites due to high shear stress, which exhibits shear-stress sensitivity. The implementation of the project is expected to obtain a shear-stress sensitive drug carrier for target treatment of AS. Drug delivery system can eliminate the adverse effect on the absorption, distribution and trans-membrane transport processes caused by the physical and chemical properties of DMY, which may increase the anti-atherosclerosis effect of DMY. It provide a new research method to thoroughly understand the role of anti-atherosclerosis mechanism of effective constituents in traditional Chinese medicine on cellular and molecular levels.

英文关键词： drug delivery;nanogels;Pickering emulsion;shear-stress sensitive;atherosclerosis