Dependence of norfloxacin diffusion across bilayers on lipid composition
Publication Date
2015-12-15Journal Title
Soft Matter
Publisher
Royal Society of Chemistry
Volume
12
Pages
2135-2144
Language
English
Type
Article
Metadata
Show full item recordCitation
Purushothaman, S., Cama, J., & Keyser, U. F. (2015). Dependence of norfloxacin diffusion across bilayers on lipid composition. Soft Matter, 12 2135-2144. https://doi.org/10.1039/C5SM02371H
Abstract
Antibiotic resistance is a growing concern in medicine and raises the need to develop and design new drug molecules that can efficiently inhibit bacterial replication. Spurring the passive uptake of the drug molecules is an obvious solution. However our limited understanding of drug–membrane interactions due to the presence of an overwhelming variety of lipids constituting cellular membranes and the lack of facile tools to probe the bio-physical interactions between drugs and lipids imposes a major challenge towards developing new drug molecules that can enter the cell via passive diffusion. Here, we used a label-free micro-fluidic platform combined with giant unilamellar lipid vesicles to investigate the permeability of membranes containing mixtures of DOPE and DOPG in DOPC, leading to a label-free measurement of passive membrane-permeability of autofluorescent antibiotics. A fluoroquinolone drug, norfloxacin was used as a case study. Our results indicate that the diffusion of norfloxacin is strongly dependent on the lipid composition which is not expected from the traditional octanol–lipid partition co-efficient assay. The anionic lipid, DOPG, slows the diffusion process whereas the diffusion across liposomes containing DOPE increases with higher DOPE concentration. Our findings emphasise the need to investigate drug–membrane interactions with focus on the specificity of drugs to lipids for efficient drug delivery, drug encapsulation and targeted drug-delivery.
Sponsorship
SP and UFK acknowledge funding from an ERC starting grant, Passmembrane 261101 and an EPSRC grant GRAPHTED, EP/ K016636/1, and JC acknowledges the support from an Internal Graduate Studentship, Trinity College, Cambridge and a Research Studentship from the Cambridge Philosophical Society.
Embargo Lift Date
2300-01-01
Identifiers
External DOI: https://doi.org/10.1039/C5SM02371H
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253340
Rights
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/