title: Efficacy and safety profile of the novel antimicrobial peptide PXL150 in a mouse model of infected burn wounds.
abstract: 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 20mg/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 ≥2.5mg/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.
authors: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; SP Technical Research Institute of Sweden, Medical Device Technology, Box 857, SE-501 15 Borås, Sweden; The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Blå stråket 5, SE-413 45 Gothenburg, Sweden.
authors: Camilla
authors: C
authors: Björn
authors: FOI Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
authors: Laila
authors: L
authors: Noppa
authors: FOI Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
authors: Emelie
authors: E
authors: Näslund Salomonsson
authors: FOI Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
authors: Anna-Lena
authors: AL
authors: Johansson
authors: FOI Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
authors: Elin
authors: E
authors: Nilsson
authors: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Blå stråket 5, SE-413 45 Gothenburg, Sweden.
authors: Margit
authors: M
authors: Mahlapuu
authors: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; SP Technical Research Institute of Sweden, Medical Device Technology, Box 857, SE-501 15 Borås, Sweden. Electronic address: joakim.hakansson@sp.se.
authors: Joakim
authors: J
authors: Håkansson
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000009:adverse effects*; D058491:Bacterial Load; D002056:Burns / Q000150:complications*; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011817:Rabbits; D051381:Rats; D016896:Treatment Outcome; D014946:Wound Infection / Q000188:drug therapy*; D014947:Wounds and Injuries / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: AMP; Antimicrobial peptide; Infected burn wounds; Pseudomonas aeruginosa