Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, United States.
Mol Pharm. 2021 Jun 7;18(6):2122-2141. doi: 10.1021/acs.molpharmaceut.1c00009. Epub 2021 Apr 29.
The ability to measure the passive membrane permeation of drug-like molecules is of fundamental biological and pharmaceutical importance. Of significance, passive diffusion across the cellular membranes plays an effective role in the delivery of many pharmaceutical agents to intracellular targets. Hence, approaches for quantitative measurement of membrane permeability have been the topics of research for decades, resulting in sophisticated biomimetic systems coupled with advanced techniques. In this review, recent developments in experimental approaches along with theoretical models for quantitative and real-time analysis of membrane transport of drug-like molecules through mimetic and living cell membranes are discussed. The focus is on time-resolved fluorescence-based, surface plasmon resonance, and second-harmonic light scattering approaches. The current understanding of how properties of the membrane and permeant affect the permeation process is discussed.
测量类似药物分子的被动膜渗透能力具有重要的生物学和药学意义。值得注意的是，药物通过细胞膜的被动扩散在将许多药物递送至细胞内靶标方面发挥了有效作用。因此，定量测量膜通透性的方法已经成为研究课题数十年，由此产生了复杂的仿生系统和先进技术。在这篇综述中，讨论了用于定量和实时分析类似药物分子通过仿生和活细胞膜的膜转运的实验方法和理论模型的最新进展。重点是基于时间分辨荧光、表面等离子体共振和二次谐波光散射的方法。讨论了如何理解膜和渗透物的性质对渗透过程的影响。
