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Key points: Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility.Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity.Hydrophilic drugs may require different strategies to obtain a sustained release profile. [ABSTRACT FROM AUTHOR]

Objectives: Previously, we developed a novel double‐coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. Methods: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release. Results: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (μm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side. Conclusion: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model. Level of Evidence: N/A Laryngoscope, 134:3953–3959, 2024 [ABSTRACT FROM AUTHOR]

Introduction: Hypoxia due to sinus obstruction is a major pathogenic mechanism leading to sinusitis. The objective of the current study is to define the electrophysiologic characteristics of hypoxia in vitro and in vivo. Methods: Cystic fibrosis bronchoepithelial cells expressing wild‐type cystic fibrosis transmembrane conductance regulator (CFTR) and human sinonasal epithelial cells were exposed to 1% or atmospheric O2 for 24 h. Time‐dependent production of cytoplasmic free radicals was measured. Cells were subjected to Ussing chamber and patch clamp technique where CFTR currents were recorded in whole‐cell and cell‐attached mode for single channel studies. Indices of mucociliary transport (MCT) were measured using micro‐optical coherence tomography. In a rabbit hypoxic maxillary sinus model, tissue oxygenation, relative mRNA expression of HIF‐1α, pH, sinus potential difference (SPD), and MCT were determined. Results: Ussing chamber (p < 0.05), whole‐cell (p < 0.001), and single channel patch‐clamp (p < 0.0001) showed significant inhibition of Cl− currents in hypoxic cells. Cytoplasmic free radicals showed time‐dependent elevation peaking at 4 h (p < 0.0001). Airway surface liquid (p < 0.0001), periciliary liquid (p < 0.001), and MCT (p < 0.01) were diminished. Co‐incubation with the free radical scavenger glutathione negated the impact of hypoxia on single channel currents and MCT markers. In sinusitis rabbits, mucosa exhibited low tissue oxygenation (p < 0.0001), increased HIF1α mRNA (p < 0.05), reduced pH (p < 0.01), and decreased MCT (p < 0.001). SPD measurements demonstrated markedly diminished transepithelial Cl− transport (p < 0.0001). Conclusion: Hypoxia induces severe CFTR dysfunction via free radical production causing reduced MCT in vitro and in vivo. Improved oxygenation is critical to reducing the impact of persistent mucociliary dysfunction. [ABSTRACT FROM AUTHOR]

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 < 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/NaHCO3− nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Key points: Duplicated images in research articles erode integrity and credibility of biomedical science.Forensic software is necessary to detect figures with inappropriately duplicated images.This analysis reveals a significant issue of inappropriate image duplication in our field. [ABSTRACT FROM AUTHOR]