Morbidity and mortality in cystic fibrosis (CF) patients is primarily attributable to persistent pulmonary infection caused by Pseudomonas aeruginosa (Pa). Over the past 12 years, work from many research groups have shown that Gallium (Ga3+) inhibits Pa growth, acting as an iron mimetic. The perspective of bringing Ga3+-based anti-Pa therapies to the clinic has recently been substantiated by initial clinical trials (NCT 01093521 and NCT 02354859) showing favourable pharmacokinetics, safety and tolerability profiles of intravenously administered Ganite® [Ga(NO3)3], a compound approved by FDA for other indications. in CF patients chronically infected by P. aeruginosa. The main objective of the present project is to provide evidence of in vivo antibacterial activity of novel inhalable Ga3+formulations, in order to gain essential pre-clinical insights for the delivery of improved/novel Ga3+-based drugs to the clinic. Ga3+ will be formulated as inhalable dry powders embedding Ga(III)-loaded sustained release nanoparticles (NPs). The experimental activity is organized in four tasks: i) the anti-P. aeruginosa activity of selected Ga3+ formulations on a representative collection of P.aeruginosa CF isolates; ii) the property of Ga3+ formulations to reduce inflammation in human white blood cells; iii) the toxicity and bio-distribution of Ga3+ formulations, after administration (intratracheal or nasal instillation) in mice; iv) the protective efficacy of Ga3+ formulations after single intratracheal administration or multiple intranasal instillations of Ga3+ in mice bearing P. aeruginosa infections. The project will foster future clinical application of Ga(III) inhalable formulations for the treatment of P. aeruginosa chronic lung infection in CF patients.