TIRF Microscopy‐Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica
| Autor: | Paul Joyce, Shakhawath Hossain, Per Larsson, Christel A. S. Bergström, Silver Jõemetsa, Simon Isaksson, Fredrik Höök |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
total internal reflection fluorescence
02 engineering and technology 010402 general chemistry 01 natural sciences Catalysis Permeability Cell membrane 03 medical and health sciences Membrane Lipids Pharmaceutical Sciences membrane permeation medicine Pharmacokinetics mesoporous silica Lipid bilayer 030304 developmental biology 0303 health sciences Total internal reflection fluorescence microscope 010405 organic chemistry Chemistry Communication General Chemistry General Medicine Mesoporous silica Permeation 021001 nanoscience & nanotechnology Silicon Dioxide supported lipid bilayer Farmaceutiska vetenskaper Communications 0104 chemical sciences Membrane medicine.anatomical_structure Microscopy Fluorescence Pharmaceutical Preparations Drug delivery drug delivery Biophysics membrane permation Mesoporous material 0210 nano-technology Drug Delivery Porosity |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| Popis: | There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biologically active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a ≈500 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small‐molecule model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behaviour of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8‐facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system‐induced changes to cellular membrane permeation. A unique angle: A new approach for monitoring the real‐time permeation of drug molecules, from the bulk phase, across a lipid membrane was established by supporting a lipid bilayer on mesoporous silica thin films. Through the use of TIRF microscopy, the angle of incidence of illumination light could be controlled to ensure the resulting evanescence was restricted within the thin film, and thus, only drug permeating the bilayer was resolved. |
| Databáze: | OpenAIRE |
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