离子互补型纳米自组装短肽与水难溶性药物的相互作用和控释研究

项目名称： 离子互补型纳米自组装短肽与水难溶性药物的相互作用和控释研究

项目编号： No.31460246

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 唐富山

作者单位： 遵义医科大学

项目金额： 48万元

中文摘要： 离子互补型纳米自组装短肽具有两亲性，并可在生理条件下形成水凝胶，其内在特性可通过氨基酸残基替换而加以调控，因而具备作为药物载体材料的潜力。拟通过系统替换RAD16-I中的疏水氨基酸，设计合成侧链疏水性不同的系列短肽，先以电镜、荧光分光光度法、原子力显微镜等研究系列短肽与模式疏水化合物芘的相互作用；探讨短肽对大黄素在水性体系中的稳定和增溶机制；考察短肽和大黄素形成胶体混悬液以及水凝胶的情形并加以表征；比较侧链疏水性不同的纳米自组装短肽所形成的水凝胶中大黄素的体外控释和体内、外抗菌、抗肿瘤作用差异。该研究将有助于明确离子互补型纳米自组装短肽稳定疏水性药物的机制，这对促进自组装短肽药物载体材料开发和疏水性药物剂型改良均有重要的理论和实践指导价值。

中文关键词： 药物载体；药物释放；离子互补型自组装短肽；疏水性药物；疏水相互作用

英文摘要： Ionic-complementary self-assembling peptides possess the potential of drug carrier for their amphiphilic property and being able to promptly self-assemble into hydrogels under physiological conditions. Their inherent properties can be regulated by changing their amino acid residues. Three novel self-assembling peptides with different hydrophobic lateral chains will be designed and synthetized on the basis of RAD16-I. The interactions between these peptides and model hydrophobic compound, pyrene, will be investigated through electron microscope, fluorospectrophotometry and atomic force microscope, respectively. Moreover, most efforts will be focused on the performance as well as the related mechanism of these peptides to stabilize emodin in aqueous system. Then, the colloidal suspensions of emodin with these peptides will be prepared in water under mechanical stirring and in-situ hydrogels will be established by adding proper amounts of the suspensions into phosphate buffers or liquid cell culture media. Following that, the controlled release of emodin in the hydrogels as well as antibacterial and antitumor effects will be investigated in vitro, respectively. Lastly, the antitumor effects of emodin in some selected hydrogels will also be investigated in vivo. These work will contribute to ascertain the mechanism through which self assembling peptides stabilize hydrophobic drugs. This will be of great value to study self assembling peptides and to develop new formulations of hydrophobic drugs. The practice of developing self assembling peptides as hydrophobic drug carriers will be greatly promoted by the colloidal suspension-in situ hydrogel system established in this research.

英文关键词： drug carrier;controlled release;ionic-complementary self-assembling peptide;hydrophobuc drug;hydrophobic interaction