玉米醇溶蛋白修饰改性制备抗癌药物输送系统的研究

项目名称： 玉米醇溶蛋白修饰改性制备抗癌药物输送系统的研究

项目编号： No.21476086

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 有机化学

项目作者： 江燕斌

作者单位： 华南理工大学

项目金额： 90万元

中文摘要： 玉米醇溶蛋白(Zein)具有可再生性、无毒性及良好的生物相容性、自组装性、疏水性和生物可降解等优点，是目前药物载体研究的热点。但Zein在载药量、载药效率、控缓释性、及药物活性靶向性等方面存在缺陷。本项目拟有针对性地通过物理和化学法对Zein进行修饰改性，包括叶酸-Zein合成，引入磁性纳米粒子、大豆卵磷脂和壳聚糖等，以克服其上述缺陷，并研究其修饰改性后的理化和生化性质；以紫杉醇、喜树碱衍生物等为抗癌模型药物，构建超声透析法和SAS+GAS法等高效制备方法制备Zein-DDS；结合现代表征技术和药物释放实验、细胞实验等测试和分析手段，对所制备的Zein-DDS进行性能评价，探索和建立DDS制备过程-微结构-性能关系，以指导性能优异的Zein-DDS的定制。本项目具有很好的前瞻性和创新性，预期研究结果可为Zein修饰改性和抗癌DDS制备提供理论和技术支撑，具有重要的理论意义和应用价值。

中文关键词： 玉米醇溶蛋白；修饰改性；抗癌药物；药物输送系统；构效关系

英文摘要： Zein, one of the natural and edible biomacromolecules in plant, is renewable, nontoxic, biocompatible, self-assembly, hydrophobic and biodegradable. Recently, study of using Zein as carrier for drug delivery systems (DDS) becomes popular. However, Zein is imperfect in drug loading, encapsulation efficiency, release behavior, target behavior and pharmaceutical activity. In this proposal, targeted physical and chemical methods, i.e. synthesis of folate-Zein, addition of magnetic nanoparticles, soy lecithin and chitosan, are used for the modification of Zein to overcome its shortages, also its physicochemical and biochemical properties are characterized after modification. Typical anti-cancer medicines, i.e., paclitaxel, camptothecin and their ramifications, are selected as model pharmaceuticals, and the efficient preparation methods, i.e. ultrasonic dialysis method, and supercritical anti-solvent coupled with gas anti-solvent process, are established to prepare Zein-DDS. The obtained Zein-DDS performances are evaluated by combining modern characterization techniques with drug release test and cells experiments, and the relationships among DDS preparation process, micro-structures and performances will be put forward and validated to guide the preparation of tailored Zein-DDS. The results are promising for the enhancement of theoretical basis and methods of Zein modification and Zein-DDS preparation.

英文关键词： Zein;modification;anti-cancer agent;drug delivery system;QSPR