基于分子动力学模拟的中药脂质纳米载体经皮促透机理及转运特性研究

Nanocarriers have become an important means of promoting percutaneous absorption of drugs, but the molecular mechanisms of transdermal and transport processes in vivo are still unclear. Our group has established a multi-layer structure mathematical model of transdermal delivery of Tripterygium glycosides, and successfully simulated the dynamics process of its diffusion and absorption in the skin. On this basis, the project proposes a new idea that combination multi-scale computer simulation and experimental practices based on molecular dynamics simulations. The transdermal delivery lipid nanocarriers particle model and the stratum corneum lipid membrane model will be established with triptolide as a model drug. The molecular dynamics simulations will be used to investigate the interactions between the lipid nanoparticles and the stratum corneum from the microscopic and mesoscopic scale, which can intuitively and dynamically describe the dynamic process of lipid nanocarriers through the skin. Different types of triptolide lipid nanocarriers (TPL-NPs) will be prepared and their transdermal properties and the effects on the skin structure in vitro will be evaluated. The experimental results and the computer simulation results will be comparative analyzed to clarify the mechanisms of percutaneous penetration enhancement and transdermal transport properties in vivo of lipid nanocarriers..This project will provide a new method for the research and development of transdermal drug delivery of TCM. It has important theoretical and practical significances for the clarification of the molecular mechanisms of percutaneous penetration enhancement and for the design and development of new formulations for transdermal delivery systems.

纳米载体已成为促进药物经皮吸收的重要手段，但其促透的分子机制和体内转运过程尚不清楚。课题组前期已建立了中药雷公藤多苷经皮给药的多层结构数学模型，成功模拟了其在皮肤中扩散吸收的动力学过程。在此基础上，本项目提出基于分子动力学模拟的计算机仿真与实验研究相结合的多尺度研究新思路，以雷公藤甲素为模型药物，构建经皮给药脂质纳米载体颗粒模型和角质层脂质膜模型，采用分子动力学模拟从微观和介观尺度考察脂质纳米颗粒与皮肤角质层的相互作用，直观、动态的描述脂质纳米载体透过皮肤的动力学过程；构建不同类型的雷公藤甲素经皮脂质纳米载体（TPL-NPs），评价TPL-NPs体外透皮特性和对皮肤结构的影响。将实验结果与计算机模拟结果对比分析，阐明脂质纳米载体经皮给药的促透机理和体内转运特性。本项目可为中药经皮给药基础研究提供新方法，对于阐明纳米载体经皮给药的促透机理，设计和开发新型经皮给药制剂具有重要的理论和实践意义。