Doroudian Mohammad, O'Neill Andrew, O'Reilly Ciaran, Tynan Aisling, Mawhinney Leona, McElroy Aoife, Webster Shanice S, MacLoughlin Ronan, Volkov Yuri, E Armstrong Michelle, A O'Toole George, Prina-Mello Adriele, C Donnelly Seamas
Department of Clinical Medicine, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, NH 03755, USA.
Nanomedicine (Lond). 2020 Dec;15(30):2933-2953. doi: 10.2217/nnm-2020-0344. Epub 2020 Nov 26.
Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. : In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake. 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 biofilm formation on airway epithelial cells. This represents a potential novel adjunctive therapy for the treatment of infection in cystic fibrosis.
巨噬细胞移动抑制因子(MIF)是一种促炎细胞因子,已被证明会加重囊性纤维化的疾病严重程度。在本研究中,我们制备并表征了负载有SCD-19(一种MIF互变异构酶活性抑制剂)的雾化载药纳米颗粒。雾化纳米颗粒具有适合肺部深部沉积的最佳液滴尺寸分布,具有高度的生物相容性和显著的细胞摄取能力。我们首次开发了一种针对MIF酶活性的雾化纳米制剂,该制剂可显著降低巨噬细胞的炎症反应,并抑制气道上皮细胞上生物膜的形成。这代表了一种治疗囊性纤维化感染的潜在新型辅助疗法。