磷脂双层疏水区限域溶胶-凝胶过程复合脂质体制备新方法及界面行为研究

Based on self-assembled structure of the phospholipid bilayer and the interfacial interaction of hydrophilicity and hydrophobicity with organosiloxane, combined with the literature at home and abroad and the foundation work of our group engaged in the molecular aggregation behavior of organosilanol and silica growth directed by liposome "outer" surface, a new route to liposil formation is proposed using lipid bilayer hydrophobic domain to confine sol-gel process of organosiloxane, aiming at improving the stability performance of the liposome as nanoparticles drug delivery system. To reveal the interactive mechanism, a model of supported lipid bilayer and an amplification experiment for oil/water interface are designed. The characterization methods mainly include fluorescent probe (label) technology and fluorescence anisotropy, low-temperature DSC, LB film balance combined with AFM, electrochemical performance test, 29Si, 31P NMR, et.al. The research is mainly focused on (1) the confined mechanism of the lipid bilayer to organosiloxane; (2) the permeation behavior of water through lipid bilayer; (3) the dynamics characteristics of sol-gel process under confined conditions at the interface. Based on the above results, the reaction model of "confinement - penetration - hydrolysis - silicification" should be established. To systematically study the formation principles of coassembly, different types of phospholipid molecules and organosiloxane precursor are chosen. The impact factors, which drive coassembly formation including the effect of solvent, structure matching of organosilanol and phospholipids, concentration ratio, et.al. , should be studied and elucidated. Based on explicit conclusion of interfacial interaction between all components in collaborative assembly, the preparation of various functional hybrid liposomes would be carried out by constructing pre-assembly, including the preparation light-controlled-release and light-harvesting liposomes, realizing the universality and applicability of the new method.

基于磷脂双层自组装结构及其界面与有机硅相互作用，结合国内外文献报道以及课题组前期从事有机硅醇分子簇集行为和脂质体“外”界面沉积氧化硅研究的工作基础，提出利用磷脂双层疏水区限域溶胶-凝胶过程制备复合脂质体新思路，以提高脂质体纳米载药系统的稳定性能。通过设计支撑脂双层模型、放大油/水界面实验，利用荧光探针光物理技术、低温DSC、LB膜天平结合AFM、电化学性能测试、29SiNMR、31PNMR、ATR-FTIR等技术手段重点研究磷脂双层疏水区对有机硅的限域机制、界面水渗透原理以及有机硅在界面限域条件下的溶胶-凝胶过程动力学特点。建立“限域-渗透-水解-硅化”反应模型。选择不同类型磷脂分子和有机硅前驱体，通过考察溶剂效应、有机硅醇与磷脂结构匹配性、浓度比例等多种因素驱动磷脂与有机硅醇协同组装，系统研究共组装体的形成规律。利用新方法设计制备光控释、捕光释氧复合脂质体等，拓展新方法的普适性和应用性。

本项目围绕提高脂质体稳定性能这一课题开展了一系列工作，结合国内外文献报道以及课题组前期从事有机硅醇分子簇集行为和脂质体“外”界面沉积氧化硅研究的工作基础，揭示了基于磷脂双层自组装结构及其界面与有机硅相互作用的分子机制，利用磷脂双层疏水区限域溶胶-凝胶过程制备了一系列复合脂质体。项目执行过程中，设计了支撑脂双层模型、放大油/水界面实验，利用荧光探针光物理技术、低温DSC、LB 膜天平结合AFM、电化学性能测试、ATR-FTIR等技术手段重点研究了磷脂双层疏水区对有机硅的限域机制、界面水渗透原理以及有机硅在界面限域条件下的溶胶-凝胶过程的动力学特点，建立了“限域-渗透-水解-硅化”反应模型。选取了不同类型有机硅前驱体，得到了溶剂效应、有机硅醇与磷脂结构匹配性、浓度比例等多种因素驱动磷脂与有机硅醇协同组装的内在规律。利用该新方法设计制备了二氧化钛加固型、捕光释氧型复合脂质体等一系列新型脂质体。拥有自主知识产权，申请（已授权）相关专利7件，包括自主研发了小型测试仪器。本项目的实施为功能复合脂质体的构筑提供了简易可行的思路和普适性的新方法，有助于高稳定性、新功能复合脂质体的规模化生产和纳米载药系统的开发。