In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate

Jlenia Brunetti, Chiara Falciani, Giulia Roscia, Simona Pollini, Stefano Bindi, Silvia Scali, Unai Cossio Arrieta, Vanessa Gomez-Vallejo, Leila Quercini, Elisa Ibba, Marco Prato, Gian Maria Rossolini, Jordi Llop, Luisa Bracci, Alessandro Pini

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A synthetic antimicrobial peptide was identified as a possible candidate for the development of a new antibacterial drug. The peptide, SET-M33L, showed a MIC90 below 1.5 μM and 3 μM for Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively. In in vivo models of P. aeruginosa infections, the peptide and its pegylated form (SET-M33L-PEG) enabled a survival percentage of 60-80% in sepsis and lung infections when injected twice i.v. at 5 mg/Kg, and completely healed skin infections when administered topically. Plasma clearance showed different kinetics for SET-M33L and SET-M33L-PEG, the latter having greater persistence two hours after injection. Bio-distribution in organs did not show significant differences in uptake of the two peptides. Unlike colistin, SET-M33L did not select resistant mutants in bacterial cultures and also proved non genotoxic and to have much lower in vivo toxicity than antimicrobial peptides already used in clinical practice. The characterizations reported here are part of a preclinical development plan that should bring the molecule to clinical trial in the next few years.

Original languageEnglish
Article number26077
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - May 12 2016

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Peptides
Pharmaceutical Preparations
Pseudomonas aeruginosa
Colistin
Pseudomonas Infections
Klebsiella pneumoniae
Infection
Sepsis
In Vitro Techniques
Clinical Trials
Lung
Skin
Injections

ASJC Scopus subject areas

  • General

Cite this

In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate. / Brunetti, Jlenia; Falciani, Chiara; Roscia, Giulia; Pollini, Simona; Bindi, Stefano; Scali, Silvia; Arrieta, Unai Cossio; Gomez-Vallejo, Vanessa; Quercini, Leila; Ibba, Elisa; Prato, Marco; Rossolini, Gian Maria; Llop, Jordi; Bracci, Luisa; Pini, Alessandro.

In: Scientific Reports, Vol. 6, 26077, 12.05.2016.

Research output: Contribution to journalArticle

Brunetti, J, Falciani, C, Roscia, G, Pollini, S, Bindi, S, Scali, S, Arrieta, UC, Gomez-Vallejo, V, Quercini, L, Ibba, E, Prato, M, Rossolini, GM, Llop, J, Bracci, L & Pini, A 2016, 'In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate', Scientific Reports, vol. 6, 26077. https://doi.org/10.1038/srep26077
Brunetti, Jlenia ; Falciani, Chiara ; Roscia, Giulia ; Pollini, Simona ; Bindi, Stefano ; Scali, Silvia ; Arrieta, Unai Cossio ; Gomez-Vallejo, Vanessa ; Quercini, Leila ; Ibba, Elisa ; Prato, Marco ; Rossolini, Gian Maria ; Llop, Jordi ; Bracci, Luisa ; Pini, Alessandro. / In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate. In: Scientific Reports. 2016 ; Vol. 6.
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