中文摘要
药物对生物体的作用首先反映在其对生物膜的作用上,考虑到生物膜特有的类脂双分子层结构和天然生物膜的复杂性,本项目以固体支撑双层类脂膜或脂质体为模拟生物膜体系,研究手性药物对模拟生物膜的影响和作用机理。本项目应用电化学方法研究了异丙酚、联萘酚、左氧氟沙星与双层类脂膜相互作用,获得了它们对双层类脂膜渗透性的影响规律性。研究了Gemini两亲分子在气液界面的Langmuir铺展膜的结构和相行为,以及它们与双层类脂膜模拟生物膜以及Fe3O4、TiO2、CdTe纳米粒子的相互作用,Gemini两亲分子在气液界面上通过诱导作用将纳米粒子图案化,建立了Gemini分子与纳米粒子之间相互作用机理模型。通过紫外-可见吸收光谱、荧光光谱、核磁共振和圆二色谱等手段研究异丙酚、联萘酚、紫草素、氟比洛芬手性化合物/药物对脂质体模拟生物膜的影响及其相互作用,取得了产生微孔通道的初步证据,获得了手性化合物/药物在脂质体模拟生物膜中的定位排列方式及其对脂质体双层类脂膜的微极性、流动性及渗透性的影响规律性,这些研究成果为脂质体载药系统的研制与开发提供启示。
英文摘要
The effect of chiral drugs on the organism is firstly realized by their action with biomembranes, taking into account the biomembrane's own structures similar to the bilayer lipid membranes and the complexity of natural biomembranes, in this project, supported bilayer lipid membranes or liposomes will be used as model biomembrane systems for the studies of the effect and action mechanism of chiral drugs on model biomembranes. Using the electrochemical methods to study the interaction of bilayer lipid membranes with Propofol, Binaphthol and Levofloxacin, the regularity of their effect on the permeation of bilayer lipid membranes was clarified. We investigated the structures and phase behavior of Langmuir films of a series of Gemini amphiphilic molecules at the air/water interface and their interaction with bilayer lipid membranes, model biomembranes and nanoparticles of Fe3O4, TiO2 and CdTe. The action mechanism model of Gemini amphiphilic molecules and nanoparticles has been built, which is that Gemini amphiphilic molecules at the air/water interface pattern the inorganic nanoparticles by induction. Using the UV-vis spectroscopy, fluorescence spectroscopy, HNMR and circular dichroism to study the effect and interaction of liposome model biomembrane with chiral compounds/drugs including Propofol, Binaphthol, Shikonin and Flurbiprogen, the evidences of producing microchannel and regularities of chiral compounds/drugs' location and arrangement on liposome model biomembrane and their effect on the micropolarity, fluidity and permeation of liposome bilayer lipid membranes were obtained. These research results benefit the research and development of liposome drug-loading systems.
结题摘要
药物对生物体的作用首先反映在其对生物膜的作用上,考虑到生物膜特有的类脂双分子层结构和天然生物膜的复杂性,本项目以固体支撑双层类脂膜或脂质体为模拟生物膜体系,研究手性药物对模拟生物膜的影响和作用机理。本项目应用电化学方法研究了异丙酚、联萘酚、左氧氟沙星与双层类脂膜相互作用,获得了它们对双层类脂膜渗透性的影响规律性。研究了Gemini两亲分子在气液界面的Langmuir铺展膜的结构和相行为,以及它们与双层类脂膜模拟生物膜以及Fe3O4、TiO2、CdTe纳米粒子的相互作用,Gemini两亲分子在气液界面上通过诱导作用将纳米粒子图案化,建立了Gemini分子与纳米粒子之间相互作用机理模型。通过紫外-可见吸收光谱、荧光光谱、核磁共振和圆二色谱等手段研究异丙酚、联萘酚、紫草素、氟比洛芬手性化合物/药物对脂质体模拟生物膜的影响及其相互作用,取得了产生微孔通道的初步证据,获得了手性化合物/药物在脂质体模拟生物膜中的定位排列方式及其对脂质体双层类脂膜的微极性、流动性及渗透性的影响规律性,这些研究成果为脂质体载药系统的研制与开发提供启示。
