Mohammad Doroudian1, Andrew O'Neill1, Ciaran O'Reilly1, Aisling Tynan1, Leona Mawhinney1, Aoife McElroy1, Shanice S Webster2, Ronan MacLoughlin3,4,5, Yuri Volkov6,7,8, Michelle E Armstrong1, George A O'Toole2, Adriele Prina-Mello6,7,9, Seamas C Donnelly10. 1. Department of Clinical Medicine, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. 2. Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, NH 03755, USA. 3. Aerogen, IDA Business Park, Dangan, Galway, Ireland. 4. School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons, Dublin, Ireland. 5. School of Pharmacy & Pharmaceutical Sciences, Trinity College, Dublin, Ireland. 6. Laboratory for Biological Characterization of Advanced Materials (LBCAM), Department of Medicine, Trinity College Dublin, Ireland. 7. Nanomedicine Group, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Ireland. 8. Department of Histology, Cytology & Embryology, First Moscow State Sechenov Medical University, Russian Federation. 9. CRANN Institute & AMBER Centre, Trinity College Dublin, Ireland. 10. Department of Medicine, Tallaght University Hospital & Trinity College Dublin, Ireland.
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.
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.
Authors: Huzaifa Adamali; Michelle E Armstrong; Anne Marie McLaughlin; Gordon Cooke; Edward McKone; Christine M Costello; Charles G Gallagher; Lin Leng; John A Baugh; Günter Fingerle-Rowson; Richard J Bucala; Paul McLoughlin; Seamas C Donnelly Journal: Am J Respir Crit Care Med Date: 2012-05-16 Impact factor: 21.405
Authors: J L Burns; R L Gibson; S McNamara; D Yim; J Emerson; M Rosenfeld; P Hiatt; K McCoy; R Castile; A L Smith; B W Ramsey Journal: J Infect Dis Date: 2000-12-27 Impact factor: 5.226