基于天然材料的多功能膜控型纳米给药系统的构建及示踪评价

In order to solve the side effect of off-target, premature release, weak selectivity existing in nano-delivery systems and the problem of poor chemotherapy effect, considering the superiority of biocompatibility and physiological responsibility of natural materials in drug delivery, the project plan to design a functional membrane switch modifying nano-drug "Warehouse", to reach multifunctional integration of targeting and multiple stimuli response in drug delivery and effectively resolve the issues of the off-target or the missing release, to improve the effectiveness of the delivery system, finally to form scientific basis and result for improving the anti-cancer drug therapeutic effect. The fundamental issue of this project to resolve is the drug intelligent release under the control of membrane, with the nano mesoporous silica (MSN) as a drug "Warehouse" model and doxorubicin as a drug model, which includes the selection and fabrication of natural materials, design of functional membrane switch and the optimization of membrane preparation, the structural characteristics of nano-composites, the feature of release kinetics under the control of membrane and so on. Combined with the imaging tracing of quantum dots, the drug delivery behavior and the antitumor behavior of the membrane-controlled nano-drug delivery system will be preliminary evaluated by in vitro and in vivo experiments. The research will provide theoretical basis for the design and preparation of the novel membrane-controlled nano-drug delivery system.

针对现有纳米给药系统存在的易脱靶、过早释放或选择性不强等因素而造成的毒副作用和治疗效果低下的难题，本项目拟设计一种基于天然材料的开关膜修饰纳米药物“仓库”，借助天然材料良好的生物相容性及生理响应性的优势，以期实现药物传输系统的靶向与刺激响应性的多功能化集成，有效地解决脱靶或漏释等问题，提高传输体系的有效性，为改善抗癌药物靶向效果提供科学依据。本项目要解决的根本问题就是膜调控下的药物智能化释放，并以纳米介孔二氧化硅（MSN）作为药物“仓库”，阿霉素为模型抗癌药物，主要的研究内容包括：天然材料优选及改性、开关膜的构建及工艺优化、纳米复合物的结构表征、药物分子受膜开关控制下释药动力学特性等研究。并结合量子点的示踪成像功能，通过体内外实验初步评价该膜控型纳米给药系统的药物输送行为及抗肿瘤有效性。研究结果将为新型膜控型纳米给药系统的设计与制备提供参考。

基于纳米介孔硅和天然高分子材料在药物传输体系的领域取得了一些研究进展。完成了纳米介孔硅的合成修饰及表征，建立了基于天然材料的开关膜控型纳米给药系统，提高抗癌药物输送的选择性和准确性，避免了漏释和脱靶现象。通过体外实验初步评价该膜控型纳米给药系统的药物输送行为及抗肿瘤有效性。此研究将为新型膜控型纳米给药系统的设计与制备提供参考。同时，将纳米介孔硅材料与天然高分子材料结合，充分利用纳米介孔硅的药物负载功能与天然高分子凝胶材料的缓释功能制备了一种基于有机无机材料优势互补的新型药物缓控释系统，该系统能够进一步改善药物的突释和漏释现象，具有潜在的开发和应用前景。另外，利用天然高分子材料在制备药物输送材料中的无毒、可降解性，生物相容性好，安全高等优点，制备了一系列以水凝胶为制剂形式的药物缓释系统。以海藻酸和羧甲基壳聚糖为原料，制备了两种物理交联体系的互穿网络水凝胶，以茯苓多糖及其羧甲基衍生物制备了具有pH敏感性的水凝胶，同时为了增加水凝胶体系的稳定性，还制备了外层聚电解质膜包衣的复合水凝胶体系。这些水凝胶体系展示出了良好的环境响应性及药物缓释的特点。