基于多级孔结构SiO2构筑具有双重环境响应性药物控释智能材料的制备与表征

介孔SiO2纳米颗粒（MSN）被认为是重要的药物缓释载体之一，但迫切需要解决其"惰性"。本项目从结构设计与表征出发，将分形维数概念和分形几何理论运用到药物控释研究中，结合其他分析方法，以多尺度多维化MSN为核，对pH和温度具有双重响应聚合物（SRP）为壳，通过聚合技术，以盐酸阿霉素，盐酸米托蒽醌，氟脲嘧啶，西咪替丁和紫杉醇为模型药物，设计和制备出具有包覆结构的环境响应性药物控释智能材料。系统研究多尺度多维化MSN和SRP结构信息，调控措施和组装条件对载药量以及智能释放的影响，旨在实现多级孔的合理搭配，从而提高药物的装载量，澄清MSN表面官能团和SRP中亲水/疏水链的影响规律；提出吸附与扩散机制，藉此能够准确了解其 "智能"行为；揭示构效关系和控释本质；发展分形技术，为研发新型智能材料提供新的视角和思路。最终为解决药物控释材料关键技术以及在相关领域中的应用提供重要的理论依据和实验指导。

Since the discovery of M41S mesoporous silica in 1992, mesoporous silica nanoparticles (MSN) have attracted numerous studies. However, normal MSN are unintelligent materials for the controllable release. To overcome the shortcoming, this project focuses on the introduction of advanced fractal dimension of concept and fractal geometry theory into the environmental response drug controlled release system, combined with other various characterization methods. By using temperature and pH dual-stimuli-responsive polymer (SRP) as shell and multi-scale dimension and hierarchical MSN as core, novel intelligent drug controlled delivery nanomaterials with environmental dual-stimuli-responsive properties and core/shell structure characteristic are designed and then prepared via polymerization technology by using Doxorubicin, Mitoxantrone, Fuorourac, Cimetidine and Taxol as drug model respectively.In the carrier system, the organic-functionally modified MSN is used as drug containers and the SRP grafted on the outside surface of MSN is employed as stimuli responsive switchable gates..In view of the above key sciences and important technologies, the multi-scale dimension and hierarchical MSN and the SRP are systematically researched including their structure morphology, surface defects, mesopores features and cross-linking networks. Meanwhile, the structurally controlled strategies of the mentioned above MSN and the assemble preparation conditions of adjusting hydrophilic/hydrophobic compositions of SRP are demonstrated, in which, particularly, their influence of loaded drug amount and the dual-pH and temperature response behaviors are investigated in details. So that, the reasonable arrange of the pore structure and the diffusion mechanism of the targeted the release profiles in different medium are put forward, which is in favor of improving the drug loading amount and clarifying influences of the surface functional groups grafted on the inner mesoporous channels of MSN and the hydrophilic/hydrophobic clusters existed in the SRP structures. Moreover, not only the intelligent properties, but also the composition-structure-performances relationships could be accurately described, which is very useful to understand the essence mechanism of controlled drug delivery derived from microstructure levels..Thus, the new method based on the fractal technology and corresponding new theory about multi-scale dimension and hierarchical mesoporous structure can be further developed, new viewpoint about "intelligent" mechanism may be suggested. In summary, based on the above all experimental and research results, this project could solve key technologies to prepare the environmental response intelligent nanomaterials in controlled drug delivery fields, and provide sufficiently theoretical basis and strong technical parameters in the biological chemical and related applications such as petrochemical industry and fine chemicals.