Aerosolized drug-loaded nanoparticles targeting migration inhibitory factors inhibit Pseudomonas aeruginosa-induced inflammation and biofilm formation

针对迁移抑制因子的气雾化载药纳米粒子可抑制铜绿假单胞菌引起的炎症和生物膜形成

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作者: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

Aim

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis.

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.

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.

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