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dc.contributor.authorHo, Duy-Khiet
dc.contributor.authorde Rossi, Chiara
dc.contributor.authorLoretz, Brigitta
dc.contributor.authorMurgia, Xabier
dc.contributor.authorLehr, Claus-Michael
dc.date.accessioned2020-08-26T11:36:19Z
dc.date.available2020-08-26T11:36:19Z
dc.date.issued2020-07-22
dc.identifier.citationPharmaceutics. 2020;12(8):E691. Published 2020 Jul 22. doi:10.3390/pharmaceutics12080691.en_US
dc.identifier.issn1999-4923
dc.identifier.pmid32707837
dc.identifier.doi10.3390/pharmaceutics12080691
dc.identifier.urihttp://hdl.handle.net/10033/622419
dc.description.abstractThe search for novel therapeutics against pulmonary infections, in particular Pseudomonas aeruginosa (PA) biofilm infections, has been intense to deal with the emergent rise of antimicrobial resistance. Despite the numerous achievements in drug discovery and delivery strategies, only a limited number of therapeutics reach the clinic. To allow a timely preclinical development, a formulation should be highly effective, safe, and most importantly facile to produce. Thus, a simple combination of known actives that enhances the therapeutic efficacy would be a preferential choice compared to advanced drug delivery systems. In this study, we propose a novel combination of an anti-inflammatory agent-itaconic acid (itaconate, IA)-and an approved antibiotic-tobramycin (Tob) or ciprofloxacin (Cipro). The combination of Tob and IA at a molar ratio of 1:5 increased the biofilm eradicating efficacy in the strain PA14 wild type (wt) by ~4-fold compared to Tob alone. In contrast, such effect was not observed for the combination of IA with Cipro. Subsequent studies on the influence of IA on bacterial growth, pyocyanin production, and Tob biofilm penetration indicated that complexation with IA enhanced the transport of Tob through the biofilm. We recommend the simple and effective combination of Tob:IA for further testing in advanced preclinical models of PA biofilm infections.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectPseudomonas aeruginosaen_US
dc.subjectbiofilmsen_US
dc.subjectciprofloxacinen_US
dc.subjectinfectionsen_US
dc.subjectitaconateen_US
dc.subjectitaconic aciden_US
dc.subjecttobramycinen_US
dc.titleItaconic Acid Increases the Efficacy of Tobramycin against Biofilms.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalPharmaceuticsen_US
dc.source.volume12
dc.source.issue8
refterms.dateFOA2020-08-26T11:36:20Z
dc.source.journaltitlePharmaceutics
dc.source.countrySwitzerland


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