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Microcavity supported lipid bilayers; evaluation of drug- lipid membrane Interactions by electrochemical impedance and fluorescence correlation spectroscopy

Ramadurai, Sivaramakrishnan, Sarangi, Nirod Kumar, Maher, Seán, Mac Connell, Nicola, Bond, Alan M., McDaid, Dennis, Flynn, Damien and Keyes, Tia E. orcid logoORCID: 0000-0002-4604-5533 (2019) Microcavity supported lipid bilayers; evaluation of drug- lipid membrane Interactions by electrochemical impedance and fluorescence correlation spectroscopy. Langmuir, 35 (24). pp. 8095-8109. ISSN 0743-7463

Abstract
Many drugs have intracellular or membrane-associated targets thus understanding their interaction with the cell membrane is of value in drug development. Cell-free tools used to predict membrane interactions should replicate the molecular organization of the membrane. Microcavity array supported lipid bilayer (MSLB) platform are versatile biophysical models of the cell membrane that combine liposome-like membrane fluidity with stability and addressability. We used an MSLB herein to interrogate drugmembrane interactions across seven drugs from different classes, including non-steroidal antiinflammatories; Ibuprofen (Ibu) and Diclofenac (Dic), antibiotics; Rifampicin (Rif), Levofloxacin (Levo) and Pefloxacin (Pef), and bisphosphonates; Alendronate (Ale) and Clodronate (Clo). Fluorescence lifetime correlation spectroscopy (FLCS) and electrochemical impedance spectroscopy (EIS) were used to evaluate the impact of drug on DOPC and binary bilayers over physiologically relevant drug concentrations. Whereas FLCS data revealed Ibu, Levo, Pef, Ale and Clo had no impact on lipid lateral mobility, EIS which is more sensitive to membrane structural change, indicated modest but significant decreases to membrane resistivity consistent with adsorption but weak penetration of drugs at the membrane. Ale and Clo, evaluated at pH 5.25, did not impact the impedance of the membrane except at concentrations exceeding 4mM. Conversely, Dic and Rif dramatically altered bilayer fluidity, suggesting their translocation through the bilayer and, EIS data, showed resistivity of the membrane decreased substantially with increasing drug concentration. Capacitance changes to the bilayer in most cases were insignificant. Using a Langmuir-Freundlich model to fit the EIS data, we propose Rsat as an empirical value that reflects permeation. Overall, the data indicate that Ibu, Levo, and Pef, adsorb at the interface of the lipid membrane but Dic and Rif interact strongly, permeating the membrane core modifying the water/ion permeability of the bilayer structure. These observations are discussed in the context of previously reported data on drug permeability and Log P.
Metadata
Item Type:Article (Published)
Refereed:Yes
Additional Information:PMID: 31120755
Subjects:UNSPECIFIED
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Research Initiatives and Centres > National Centre for Sensor Research (NCSR)
Publisher:ACS Publications
Official URL:https://doi.org/10.1021/acs.langmuir.9b01028
Copyright Information:© 2019 American Chemical Society
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
Funders:Science Foundation Ireland; Grant No. [14/IA/2488], Irish Research Council, Government of Ireland; GOIPD/2014/322
ID Code:23390
Deposited On:30 May 2019 15:31 by Nirod Kumar Sarangi . Last Modified 01 Mar 2022 15:26
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