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. 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.
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
Jehangir
J
Cama
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.|Department of Mechanical and Process Engineering, ETH Zurich, CLA H 1.1 Tannenstrasse 3, 8092 Zurich, Switzerland.
Michael
M
Schaich
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.|Jacobs University Bremen, Campus Ring 1, D-28759, Bremen, Germany.
Kareem
K
Al Nahas
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
Silvia
S
Hernández-Ainsa
Department of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom.
Stefano
S
Pagliara
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, United Kingdom.
Ulrich F
UF
Keyser
D002463:Cell Membrane Permeability / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D000077422:Enrofloxacin; D004867:Equipment Design; D024841:Fluoroquinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D056656:Lab-On-A-Chip Devices; D008055:Lipids / Q000737:chemistry*; D008856:Microscopy, Fluorescence / Q000379:methods; D010713:Phosphatidylcholines / Q000737:chemistry
D024841:Fluoroquinolones; D008055:Lipids; D010713:Phosphatidylcholines; D000077422:Enrofloxacin