Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia

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 (HCO3−) topically fails due...

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Bibliographic Details
Published in:International forum of allergy & rhinology 2024-06, Vol.14 (6), p.1026-1035
Main Authors: Cho, Do Yeon, Rivers, Nicholas J., Lim, Dong‐Jin, Zhang, Shaoyan, Skinner, Daniel, Yang, Lydia, Menon, Adithya J., Kelly, Olivia Jo, Jones, Martin P., Bicknell, Brenton T., Grayson, Jessica W., Harris, Elex, Rowe, Steven M., Woodworth, Bradford A.
Format: Article
Language:English
Subjects:
Acidification
airway surface liquid
Allergic diseases
bicarbonate
Cell surface receptors
chronic rhinosinusitis
chronic sinusitis
ciliary beat frequency
Computed tomography
Confocal microscopy
Controlled release
Cystic fibrosis
Explants
Glutathione
Glycolic acid
Maxilla
Microscopy
mucociliary clearance
mucociliary transport
Mucus
nanoparticle
Nanoparticles
optical coherence tomography
periciliary liquid
Reabsorption
Respiratory diseases
Respiratory tract diseases
Rhinosinusitis
Sinus
Sinusitis
Sodium bicarbonate
Tomography
Toxicity
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Summary: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 (HCO3−) 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/NaHCO3 nanoparticles as novel strategy for CF airway disease. Methods GSH/NaHCO3 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 HCO3− 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 
ISSN:2042-6976
2042-6984
DOI:10.1002/alr.23301