中文摘要
纳米载药系统用于增加小分子水溶性药物的经皮通透性已成为新的研究热点,研究者们也提出许多对药物经皮给药透过机制行之有效的研究方法。尽管在一定程度上取得了一些进展,但尚处于初步研究阶段,还没有全面的实验方法能在细胞及整体水平上清楚阐述纳米经皮给药系统的透皮机制。在前期研究基础上,本项目基于“双标记+双细胞+可视化”的设计理念,着眼于“纳米经皮给药系统在细胞及整体水平上的透皮转运行为实时监测”这一关键环节,拟构建一种双标记纳米经皮给药可视化示踪系统,通过双细胞共培养模型研究其透皮机制;将皮肤药理学与药物分析学结合,建立一种非侵入式、实时、灵敏的荧光示踪分析方法,在细胞及整体水平上综合分析纳米载药系统与细胞膜的相互作用、药物转运及外排途径,实时监测纳米载药系统在皮肤细胞共培养模型中的动态扩散行为,全面深入地探讨纳米载药系统经皮给药的透过机制,为研究纳米载药系统经皮给药促渗机制提供一种新方法。
英文摘要
Nano-drug delivery system used to increase the percutaneous permeability of small molecular hydrophilic drug has became new research hot spot. Researchers have proposed many effective methods on the mechanism of the transdermal drug delivery. Although having made some extent progress, it was still in the stage of preliminary study. There is no comprehensive experiment method to clarify the transdermal mechanism of nano-drug delivery system on cells and the overall level clearly. Therefore, the further study about the mechanisms of absorption, uptake and efflux of nano-drug delivery system are very meaningful to interpret the behavior of nano drug delivery system in vivo. This investigation will be based on the design concept of “a co-culture cell model, a double fluorescence labeling technique and real-time visualization of monitoring”, and focused on the key link of “the transport processes of whole nano drug delivery system in a co-culture cell model”. The aim is to develop a non-invasive, real-time and sensitive fluorescent tracer analysis method combining with skin pharmacology and pharmacoanalysis. In this study, the interaction between nano-drug delivery system and cell surface will be analyzed, the pathway of endocytosis and efflux of nano-drug delivery system in cell and the dynamic characteristics of the trans-epithelial cell transport will be also investigated, respectively. Moreover, the dynamic diffusion behavior of nanoparticles drug delivery system in of skin through real-time monitoring method should be visualized. In all, comprehensive and in-depth discussion of nano-drug delivery system in cell and the overall transport mechanism will be investigated, providing a new way to study the mechanism of nano-drug delivery system used in transdermal drug delivery.
