Alessandro Pini
University of Siena, Italy
Title: A novel synthetic antimicrobial peptide for the cure of gram-negative infections: Mechanism of action, efficacy in vivo, toxicity, bio-distribution and resistance selection
Biography
Biography: Alessandro Pini
Abstract
A synthetic antimicrobial peptide was identified some years ago as possible candidate for the development of a new antibacterial drug. The peptide showed a MIC 90 below 1.5 µM for Pseudomonas aeruginosa and Klebsiella pneumonia. In models in vivo of P. aeruginosa lethal infections the peptide and its pegylated form, allowed a survival percentage ranging between 65-80% in sepsis and lung infections when injected IV, and completely resolved skin infections when administered topically. Plasma clearance demonstrated different kinetics for both peptides, with a higher persistence for the pegilated one after two hours from injection. Bio-distribution in organs did not show significant uptake differences between the two peptides. Contrary to colistin, the molecule here described did not select resistant mutants in bacterial cultures. Moreover it resulted non-genotoxic and with an in vivo toxicity comparable to antimicrobial peptides already used in clinic. The characterizations here reported are part of a preclinical development plan that should bring the molecule to clinical trials in the next years.
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