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dc.contributor.authorGraef, Florian
dc.contributor.authorVukosavljevic, Branko
dc.contributor.authorMichel, Jean-Philippe
dc.contributor.authorWirth, Marius
dc.contributor.authorRies, Oliver
dc.contributor.authorDe Rossi, Chiara
dc.contributor.authorWindbergs, Maike
dc.contributor.authorRosilio, Véronique
dc.contributor.authorDucho, Christian
dc.contributor.authorGordon, Sarah
dc.contributor.authorLehr, Claus Michael
dc.date.accessioned2018-02-19T15:43:35Z
dc.date.available2018-02-19T15:43:35Z
dc.date.issued2016
dc.identifier.citationThe bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane. 2016, 243:214-224 J Control Releaseen
dc.identifier.issn1873-4995
dc.identifier.pmid27769806
dc.identifier.doi10.1016/j.jconrel.2016.10.018
dc.identifier.urihttp://hdl.handle.net/10033/621287
dc.description.abstractGram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell®filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshBiological Availabilityen
dc.subject.meshCell Membraneen
dc.subject.meshCell Membrane Permeabilityen
dc.subject.meshGram-Negative Bacteriaen
dc.subject.meshPhospholipidsen
dc.titleThe bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane.en
dc.typeArticleen
dc.contributor.departmentHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalJournal of controlled release : official journal of the Controlled Release Societyen
refterms.dateFOA2018-06-13T00:43:02Z
html.description.abstractGram-negative bacteria possess a unique and complex cell envelope, composed of an inner and outer membrane separated by an intermediate cell wall-containing periplasm. This tripartite structure acts intrinsically as a significant biological barrier, often limiting the permeation of anti-infectives, and so preventing such drugs from reaching their target. Furthermore, identification of the specific permeation-limiting envelope component proves difficult in the case of many anti-infectives, due to the challenges associated with isolation of individual cell envelope structures in bacterial culture. The development of an in vitro permeation model of the Gram-negative inner membrane, prepared by repeated coating of physiologically-relevant phospholipids on Transwell®filter inserts, is therefore reported, as a first step in the development of an overall cell envelope model. Characterization and permeability investigations of model compounds as well as anti-infectives confirmed the suitability of the model for quantitative and kinetically-resolved permeability assessment, and additionally confirmed the importance of employing bacteria-specific base materials for more accurate mimicking of the inner membrane lipid composition - both advantages compared to the majority of existing in vitro approaches. Additional incorporation of further elements of the Gram-negative bacterial cell envelope could ultimately facilitate model application as a screening tool in anti-infective drug discovery or formulation development.


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