Aerosolized Drug-Loaded Nanoparticles Targeting Migration Inhibitory Factors Inhibit <i>Pseudomonas Aeruginosa</i> -Induced Inflammation and Biofilm Formation
Mohammad Doroudian, Andrew O’Neill, Ciaran O’Reilly, Aisling Tynan, Leona Mawhinney, Aoife McElroy, Shanice S. Webster, Ronan MacLoughlin, Yuri Volkov, Michelle E. Armstrong, George A. O’Toole, Adriele Prina‐Mello, Seamas C. Donnelly
Abstract
Aim: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. Methods: In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. Results: The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake. Conclusion: For the first time, we have developed an aerosolized nano-formulation against MIF's enzymatic activity that achieved a significant reduction in the inflammatory response of macrophages, and inhibited Pseudomonas aeruginosa biofilm formation on airway epithelial cells. This represents a potential novel adjunctive therapy for the treatment of P. aeruginosa infection in cystic fibrosis.