期刊
ANALYTICA CHIMICA ACTA
卷 1153, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.aca.2021.338296
关键词
3D printing; Cell membrane transporter; P-glycoprotein; Permeation; Real-time monitoring; Sequential injection analysis
资金
- EFSA-CDN project [CZ.02.1.01/0.0/0.0/16_019/0000841]
- ERDF
- Project of Specific Research, SVV [260 548]
- FEDER/Spanish Ministry of Science, and Innovation (MICINN) Spanish State Research Agency (AEI) [CTM2017-84763-C3-3-R]
- Division of Analytical Chemistry of the European Chemical Society
A new design of permeation module based on 3D printing was developed to monitor the interaction of exogenic compounds with cell membrane transporters in real-time. The module was shown to be effective in studying the activity of the P-glycoprotein membrane transporter and the inhibitory effect of verapamil, demonstrating enhanced Rho123 transfer and accumulation into cells. This 3D-printed module shortened permeation testing time and allowed for evaluation based on kinetic profiles, showing potential for rapid and accurate testing in drug development.
A new design of permeation module based on 3D printing was developed to monitor the interaction of exogenic compounds with cell membrane transporters in real-time. The fluorescent marker Rhodamine 123 (Rho123) was applied as a substrate to study the activity of the P-glycoprotein membrane transporter using the MDCKII-MDR1 genetically modified cell line. In addition, the inhibitory effect of verapamil (Ver), a prototype P-glycoprotein inhibitor, was examined in the module, demonstrating an enhanced Rho123 transfer and accumulation into cells as well as the applicability of the module for Pglycoprotein inhibitor testing. Inhibition was demonstrated for different ratios of Rho123 and Ver, and their competition in terms of interaction with the P-glycoprotein transporter was monitored in real-time. Employing the 3D-printed module, permeation testing was shortened from 8 h in the conventional module to 2 h and evaluation based on kinetic profiles in every 10 min was possible in both donor and acceptor compartments. We also show that monitoring Rho123 levels in both compartments enables calculate the amount of Rho123 accumulated inside cells without the need of cell lysis. (c) 2021 Elsevier B.V. All rights reserved.
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