基于角膜电氛的氨基葡聚糖类双重效应囊泡衣膜的构建及其促透作用研究

项目名称： 基于角膜电氛的氨基葡聚糖类双重效应囊泡衣膜的构建及其促透作用研究

项目编号： No.81202927

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： 张婧

作者单位： 江西中医药大学

项目金额： 23万元

中文摘要： 角膜前难滞留及角膜脂水层交替结构是药物眼前段吸收的主要屏障，研究膜修饰纳米载体是促进药物眼部吸收的热点。然而修饰后载体是否降低药物眼前清除率或/并促进其跨膜吸收、角膜电氛在诱发该双重效应中的角色及机理、制剂在靶组织的行为预测是亟待解决的关键科学问题。本课题组研究发现某些氨基葡聚糖类在角膜电氛环境下发生生物黏附，并显著促进微粒以细胞旁路途径渗透至角膜上皮细胞深层。结合脂质体对药物的高效包封及缓慢释放，本课题以电荷为标准，选择壳聚糖、壳寡糖、三甲基壳聚糖、羧甲基壳聚糖为衣膜材料；以水溶性为标准，选择具有捕获自由基且跨膜吸收障碍特征的姜黄素、矢车菊素为模型药物，通过构建新型衣膜修饰脂质体给药系统、总结衣膜-脂质-药物-给药系统-生物学效应传变规律，对衣膜双重促透作用及机制进行研究，以期指导设计膜修饰纳米载体，为高分子衣膜的构建及应用提供通用性系统性的研究模式，进一步完善眼部给药系统的制剂学理论。

中文关键词： 氨基葡聚糖类；修饰脂质体；黏膜黏附；跨膜促透；传变规律

英文摘要： Corneal epithelia alongwith the tear turnover, serve as biological barriers for the entrance of extraneous substance for topical ocular administration. The use of surface modified colloidal drug delivery system is a suitable strategy to obtain enhanced bioavailability. However, the exhibition of reduced precorneal drug loss and improved corneal permeability for modified nanocarriers and the related influence of corneal charges, and the prediction of behavior profile for nanocarriers in targeted tissue are still undetermined. Our research group found that some glycosaminoglycans exhibited a higher permeation into deeper corneal layers, especially with longer contacting time because of corneal charges. Therefore, taking advantage of the high durg encapsulation efficiency and sustained release characteristics of liposomes, we chose chitosan, chitosan oligosaccharide, N-trimethyl chitosan chloride and N-carboxymethyl chitosan as vesicle coatings according to charges, and applied curcumin and cyanidin capturing free radicals as model drugs with low permeability according to water-solubility. With the construction of novel glycosaminoglycan-coated liposomal drug delivery system, after the evaluation of dual function and the mechanism, we are assumed to guide the design of surface modified nanocarriers with the help of

英文关键词： Glycosaminoglycans；Modified liposomes；Mucoadhesive；Transcorneal permeability enhancement；Transmission rule