囊性纤维化
粘液
碳酸氢盐
医学
谷胱甘肽
粘液纤毛清除率
毒性
病理
药理学
内科学
生物化学
化学
肺
生物
生态学
酶
作者
Do‐Yeon Cho,Nicholas J. Rivers,Dong‐Jin Lim,Shaoyan Zhang,Daniel Skinner,Lydia C Yang,Adithya J. Menon,OB Kelly,Martin P. Jones,Brenton T. Bicknell,Jessica W. Grayson,Elex S. Harris,Steven M. Rowe,Bradford A. Woodworth
摘要
Abstract Introduction Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO 3 − ) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO 3 nanoparticles as novel strategy for CF airway disease. Methods GSH/NaHCO 3 poly (lactic‐co‐glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose‐release curves, surface pH, toxicity, and MCT indices using micro‐optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy. Results Sustained release of GSH and HCO 3 − with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) ( p < 0.001) and 6.87 ± 0.05 at 14 days ( p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy. Conclusion Findings suggest that GSH/NaHCO 3 − nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.
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