dc.contributor.author | Cama, J | |
dc.contributor.author | Schaich, M | |
dc.contributor.author | Al Nahas, K | |
dc.contributor.author | Hernández-Ainsa, S | |
dc.contributor.author | Pagliara, S | |
dc.contributor.author | Keyser, UF | |
dc.date.accessioned | 2017-02-13T10:39:28Z | |
dc.date.issued | 2016-09-08 | |
dc.description.abstract | Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug - we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community. | en_GB |
dc.description.sponsorship | The work was supported by an ERC Consolidator grant “DesignerPores” awarded to UFK. JC acknowledges support from the BBSRC. MS was supported by the Friedrich Naumann Foundation for Freedom and the Swiss-European Mobility Programme. KAN was supported by the Erasmus Plus student exchange programme. SHA is supported by a Herchel Smith Postdoctoral Fellowship. SP acknowledges support from the Leverhulme Trust through an Early Career Fellowship (ECF-2013-444). | en_GB |
dc.identifier.citation | Vol. 6, 32824 | en_GB |
dc.identifier.doi | 10.1038/srep32824 | |
dc.identifier.uri | http://hdl.handle.net/10871/25760 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/27604156 | en_GB |
dc.rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.title | Direct optofluidic measurement of the lipid permeability of Fluoroquinolones | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-02-13T10:39:28Z | |
dc.identifier.issn | 2045-2322 | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |
dc.identifier.pmcid | PMC5015079 | |
dc.identifier.pmid | 27604156 | |