Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones
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....
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| Published in | Scientific reports Vol. 6; no. 1; p. 32824 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Nature Publishing Group
08.09.2016
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| 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. |
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| AbstractList | 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. 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. |
| ArticleNumber | 32824 |
| Author | Al Nahas, Kareem Cama, Jehangir Pagliara, Stefano Hernández-Ainsa, Silvia Keyser, Ulrich F Schaich, Michael |
| Author_xml | – sequence: 1 givenname: Jehangir surname: Cama fullname: Cama, Jehangir organization: Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom – sequence: 2 givenname: Michael surname: Schaich fullname: Schaich, Michael organization: Department of Mechanical and Process Engineering, ETH Zurich, CLA H 1.1 Tannenstrasse 3, 8092 Zurich, Switzerland – sequence: 3 givenname: Kareem surname: Al Nahas fullname: Al Nahas, Kareem organization: Jacobs University Bremen, Campus Ring 1, D-28759, Bremen, Germany – sequence: 4 givenname: Silvia surname: Hernández-Ainsa fullname: Hernández-Ainsa, Silvia organization: Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom – sequence: 5 givenname: Stefano surname: Pagliara fullname: Pagliara, Stefano organization: Department of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom – sequence: 6 givenname: Ulrich F surname: Keyser fullname: Keyser, Ulrich F organization: Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27604156$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.3389/fimmu.2013.00280 10.1038/nprot.2009.234 10.1017/S1551929500055541 10.1016/j.ddtec.2004.11.013 10.1016/j.ejps.2005.08.007 10.1021/jacs.5b08960 10.1128/JB.01477-10 10.1039/C5SM02371H 10.1128/AAC.43.6.1511 10.1039/C4LC00217B 10.1016/S0731-7085(96)02033-X 10.1063/1.4816712 10.1016/0378-5173(92)90099-N 10.1038/nrmicro1994 10.1093/jac/28.5.639 10.2116/analsci.25.1403 10.1002/smll.201301904 10.1039/c2lc41215b 10.1021/jm00074a027 10.1021/ac201410m 10.1021/jm970530e 10.1021/jm010152k 10.1021/jm9507082 10.1146/annurev.pharmtox.41.1.443 10.1038/ncomms10447 10.1021/ac802351w 10.1128/AAC.37.7.1393 10.1021/ac901560w 10.1016/j.jconrel.2013.10.037 10.1136/gut.29.8.1035 10.1016/S0043-1354(96)00141-8 10.1128/br.27.1.87-115.1963 10.1002/jps.21068 |
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| Snippet | Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of... Abstract Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of... |
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| SubjectTerms | Antibiotic resistance Antibiotics Cell Membrane Permeability - drug effects Chemistry, Pharmaceutical - methods Data processing Drug development Equipment Design Fluoroquinolones Fluoroquinolones - chemistry Fluoroquinolones - pharmacokinetics Hydrogen-Ion Concentration Lab-On-A-Chip Devices Lipid membranes Lipids Lipids - chemistry Membrane permeability Membranes Microfluidics Microscopy, Fluorescence - methods Octanol Permeability Phosphatidylcholines - chemistry |
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| Title | Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/27604156 https://www.proquest.com/docview/1899069583/abstract/ https://search.proquest.com/docview/1818333862 https://pubmed.ncbi.nlm.nih.gov/PMC5015079 |
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