透析法制备羟基磷灰石巢状纳米球及其载药性能研究

Because of its good bioactivity and biocompatibility, as well as nano-effect, nano-hydroxyapatite is widely used in the field of biomaterials, such as hard tissue repairment, drug carriers,etc.So, preparation of functional HA nanomaterials in a simple and effective method has become the hot research topic in biomaterials feild.Nowadays,studies on biomimetic mineralization of HA are mainly focused on obtaining colloidal stable HA nanocrystals，which based on the principle of interaction between the template molecule and the inorganic minerals,such as using kinds of stablizing agents and capping agents.As far as HA nano-assembly with hierarchical nanostructures were concerned,it is seldomly reported.This application is designed to simulated organisms which using ion channels of the vesicles or cell membrane to regulate the distribution of inorganic ions, together with the auxiliary of extracellular matrix proteins to build bones,teeth and other hard tissues which having hierarchical nanostructures. Dialysis bags used here is to utilize their semi-permeable function to regulate diffusion of calcium and phosphate ions, thus, to control the nucleation sites of HA. As one of extracellular matrix components, hyaluronic acid is used as assistance of stablizing agent to build nest-like HA nanospheres.We will also examine the drug carrying performance of the obtained nest-like HA nanospheres.We believe that the idea in this application will be beneficial in uncovering the role and principle of semi-permeable membrane in biomimetic HA herarchical nanostructures by using a dialysis method.

纳米羟基磷灰石（HA）因具有良好生物活性和生物相容性的同时，兼具纳米效应, 而被广泛用于生物材料领域, 如硬组织修复、药物载体等。如何简便、有效地制备具有功能性的HA纳米材料已成为生物材料领域内的研究重点和热点。目前，对HA的仿生矿化研究主要集中在通过模板分子与无机矿物质间的相互作用来调控HA的结晶，以得到稳定分散的HA纳米晶体颗粒；而在HA纳米颗粒的组装方式以及构建复杂有序的HA功能性纳米结构方面，尚缺乏有效、可行手段。本申请旨在模拟生物体借助囊泡、细胞膜等半渗透膜上的离子通道来调控的无机离子的分布，加上膜外基质多糖的辅助，来构建骨骼、牙齿等具有复杂有序纳米结构的硬组织的原理；利用透析袋的半渗透功能来调控钙、磷离子的结晶成核位点，在膜外基质成分透明质酸的协助下，构建复杂有序HA纳米结构，并考察其载药性能。本申请有利于揭示半透膜的透析作用在仿生构建HA纳米复杂结构方面的原理和作用。

纳米磷灰石因具有良好生物活性和生物相容性的同时，兼具纳米效应, 而被广泛用于生物材料领域, 如硬组织修复、药物载体等。如何简便、有效地制备具有功能性的磷灰石纳米材料已成为生物材料领域内的研究重点和热点。然而，如何得到稳定分散的磷灰石中空纳米球，尚较少有文献报道。本项目利用透明质酸在水溶液中对离子强的络合作用来调控钙、磷离子的分布，在透析袋的辅助下构建磷灰石中空纳米球，通过不断优化反应参数，得到了平均粒径为200nm，且在水中稳定单分散的磷灰石中空纳米球，借助各项分析监测仪器对反应的过程进行监控，对产物的形貌、组分和结构进行解析，以深入研究其具体形成机制。与此同时，对所得产物开展载负抗癌药物性能的相关应用研究。. 本项目旨在模拟生物体借助囊泡、细胞膜等半渗透膜上的离子通道来调控的无机离子的分布，构建骨骼、牙齿等具有复杂有序纳米结构的硬组织的原理；利用膜外基质成分-透明质酸透来调控钙、磷离子的结晶成核位点，在透析袋的半渗透功能的协助下，构建复杂有序磷灰石纳米结构，并考察其载药性能。. 项目执行以来，已成功制备出磷灰石中空纳米颗粒，并将其应用于抗癌药物载体的应用，体外细胞培养实验结果呈现出材料具有酸度响应释放的机制。