New publication: In vitro and in vivo tests for a novel antibacterial drug candidate

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

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.

In vivo antibacterial activity of SET-M33L peptide in skin infection. Example of images of five animals at day 2.

In vivo antibacterial activity of SET-M33L peptide in skin infection. Example of images of five animals at
day 2.

Authors:

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

Source:

Brunetti, J. et al. In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate. Sci. Rep. 6, 26077; doi: 10.1038/srep26077 (2016).

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