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dc.contributor.authorPurushothaman, Sowmyaen
dc.contributor.authorCama, Jehangiren
dc.contributor.authorKeyser, Ulrichen
dc.date.accessioned2016-01-18T18:41:06Z
dc.date.available2016-01-18T18:41:06Z
dc.date.issued2015-12-15en
dc.identifier.citationPurushothaman et al. Soft Matter (2016) Vol. 12, pp. 2135-2144. doi: 10.1039/C5SM02371Hen
dc.identifier.issn1744-683X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253340
dc.description.abstractAntibiotic 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.
dc.description.sponsorshipSP 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.
dc.languageEnglishen
dc.language.isoenen
dc.publisherRoyal Society of Chemistry
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.titleDependence of norfloxacin diffusion across bilayers on lipid compositionen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5SM02371Hen
prism.endingPage2144
prism.publicationDate2015en
prism.publicationNameSoft Matteren
prism.startingPage2135
prism.volume12en
dc.rioxxterms.funderERC
dc.rioxxterms.funderEPSRC
dc.rioxxterms.projectidEP/K016636/1
rioxxterms.versionofrecord10.1039/C5SM02371Hen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-15en
dc.contributor.orcidCama, Jehangir [0000-0002-5982-1941]
dc.contributor.orcidKeyser, Ulrich [0000-0003-3188-5414]
dc.identifier.eissn1744-6848
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (EP/K016636/1)
pubs.funder-project-idEuropean Research Council (261101)
cam.orpheus.successThu Jan 30 12:55:24 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2300-01-01


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales