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Efficacy and safety profile of the novel antimicrobial peptide PXL150 in a mouse model of infected burn wounds
RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. Pergamum AB, Sweden; University of Gothenburg, Sweden.
FOI Swedish Defence Research Agency, Sweden.
FOI Swedish Defence Research Agency, Sweden.
FOI Swedish Defence Research Agency, Sweden.
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2015 (English)In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 45, no 5, p. 519-524Article in journal (Refereed) Published
Abstract [en]

The urgent need to develop novel antimicrobial therapies has stimulated interest in antimicrobial peptides as therapeutic candidates for the treatment of infectious diseases. The aim of this study was to evaluate the anti-infectious effect of the synthetic antimicrobial peptide PXL150, formulated in hydroxypropyl cellulose (HPC) gel, on Pseudomonas aeruginosa in vitro and in an in vivo mouse model of infected burn wounds as well as to assess the in vivo safety profile of PXL150 in rats and rabbits. Minimal microbicidal concentration analysis showed prominent efficacy of PXL150 against P. aeruginosa in vitro, which was further enhanced in formulating the peptide in HPC gel. Application of 1.25, 2.5, 5, 10 and 20 mg/g PXL150 in HPC gel twice daily for four consecutive days significantly reduced bacterial counts in the burn wounds compared with non-treated or placebo-treated controls. Continuous bioluminescence measurements of the bacteria revealed a pronounced anti-infective effect already at the first day post infection by PXL150 in concentrations of ≥2.5 mg/g. In the non-clinical safety studies, PXL150 showed a favourable safety profile following repeated administration systemically and locally in rats and rabbits, respectively. In conclusion, these data support that PXL150 has the potential to be an effective and safe drug candidate for the treatment of infected burn wounds. The findings encourage the progression of PXL150 as a novel topical treatment of microbial infections.

Place, publisher, year, edition, pages
2015. Vol. 45, no 5, p. 519-524
Keywords [en]
Antimicrobial peptide, AMP, Infected burn wounds, Pseudomonas aeruginosa
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-6848DOI: 10.1016/j.ijantimicag.2014.12.015PubMedID: 25649371Local ID: 23780OAI: oai:DiVA.org:ri-6848DiVA, id: diva2:964689
Available from: 2016-09-08 Created: 2016-09-08 Last updated: 2019-07-03Bibliographically approved

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