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Graef, F, Vukosavljevic, B, Michel, J-P, Wirth, M, Ries, O, De Rossi, C, Windbergs, M, Rosilio, V, Ducho, C, Gordon, S and Lehr, C-M (2016) The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane. Journal of Controlled Release, 243. pp. 214-224. ISSN 1873-4995
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The bacterial cell envelope as delimiter of anti-infective bioavailability - An in vitro permeation model of the Gram-negative bacterial inner membrane..pdf - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB) | Preview |
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Abstract
Gram-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.
| Item Type: | Article |
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| Uncontrolled Keywords: | 0903 Biomedical Engineering, 1115 Pharmacology And Pharmaceutical Sciences |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Elsevier |
| Related URLs: | |
| Date Deposited: | 09 Jun 2017 10:52 |
| Last Modified: | 04 Sep 2021 11:26 |
| DOI or ID number: | 10.1016/j.jconrel.2016.10.018 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/6677 |
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