Login (DCU Staff Only)
Login (DCU Staff Only)

DORAS | DCU Research Repository

Explore open access research and scholarly works from DCU

Advanced Search

Interaction of miltefosine with microcavity supported lipid membrane: biophysical insights from electrochemical impedance spectroscopy

Sarangi, Nirod Kumar, Prabhakaran, Amrutha and Keyes, Tia E. orcid logoORCID: 0000-0002-4604-5533 (2020) Interaction of miltefosine with microcavity supported lipid membrane: biophysical insights from electrochemical impedance spectroscopy. Electroanalysis, 32 (12). pp. 2936-2945. ISSN 1040-0397

Abstract
Miltefosine an alkylphosphocholine analogue, is the only drug taken orally for the treatment of leishmaniasis-a parasitic disease caused by sandflies. Although it is believed that Miltefosine exerts its activity by acting at the lipid membrane, detailed understanding of the interaction of this drug with eukaryotic membranes is still lacking. Herein, we exploit microcavity pore suspended lipid bilayers (MSLBs) as a biomimetic platform in combination with a highly sensitive label-free electrochemical impedance spectroscopy (EIS) technique to gain biophysical insight into the interaction of Miltefosine with host cell membrane as a function of lipid membranes composition. Four membrane compositions with increasing complexity were evaluated; DOPC, DOPC:Chol (75:25), domain forming DOPC:SM:Chol (40:40:20) and mammalian plasma membrane (MPM) mimetic DOPC:DOPE:Chol:SM:DOPS (32:25:20:15:8) and used to study the interaction of Miltefosine in a concentration-dependent manner using EIS. The membrane resistance changes in response to Miltefosine were modelled by an empirical Langmuir isotherm binding model to provide estimates of binding saturation and equilibrium association constant. Miltefosine was found to have greatest impact on electrochemical properties of the simpler membrane systems; DOPC and DOPC:Chol, where these membranes were found to be more susceptible to membrane thinning, attributed to strong permeation/penetration of the drug whilst, compositions that included both Chol and SM, expected to contain large liquid-ordered domains exhibited weaker changes to membrane resistance but strongest drug association. In contrast, at the MPM membrane, Miltefosine exerts weakest association, which is tentatively attributed to electrostatic effects from the anionic DOPS but some membrane thinning is observed reflected in change in resistance and capacitance values attributed to some weak permeation.
Metadata
Item Type:Article (Published)
Refereed:Yes
Uncontrolled Keywords:pore-suspended bio-membranes; impedance spectroscopy; lipid-drug interaction; leishmaniasis; Miltefosine; drug-permeation
Subjects:Physical Sciences > Chemistry
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:John Wiley & Sons
Official URL:http://dx.doi.org/10.1002/elan.202060424
Copyright Information:© 2020 John Wiley & Sons
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
Funders:Enterprise Ireland [grant number [CF/2017/0631], European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813920 for LogicLab ITN.
ID Code:25032
Deposited On:28 Sep 2020 12:12 by Nirod Kumar Sarangi . Last Modified 16 Sep 2021 03:30
Documents

Full text available as:

[thumbnail of Sarangi et al Manuscript R1 updated.pdf]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
800kB
Downloads

Downloads

Downloads per month over past year

Archive Staff Only: edit this record