Researchers have identified a short-sized antimicrobial peptide (AMP) from frog skin, Esc(1-21), that rapidly kills Pseudomonas aeruginosa and eradicates its biofilm with a membrane-perturbing mechanism which limits the induction of bacterial resistance. Furthermore, a diastereomer of Esc(1-21) was found to be more efficient in stimulating migration of bronchial epithelial cells and in reducing lung bacterial burden in murine models of P. aeruginosa lung infection, upon a single intratracheal (i.t.) instillation. The project will initially study the effect of the two Esc peptides on the lung epithelial permeability. A multidisciplinary approach combining biochemical, cell biology and computational methods as well as healthy mice for in vivo studies will be used. Next, polymeric nanoparticles (NPs) will be produced for delivery and sustained release of the selected AMPs at lung. The potential of clinical application of Esc peptide-loaded NPs will be evaluated by preclinical studies in mice to determine the pulmonary safety profile and host response upon their intratracheal administration.