The human tracheobronchial tree surface is covered with mucus. A healthy mucus is a heterogeneous material flowing toward the esophagus and a major defense actor against local pathogen proliferation and pollutant deposition. An alteration of mucus or its environment such as in cystic fibrosis dramatically impacts the mucociliary clearance. In the present study, we investigate the mechanical organization and the physics of such mucus in human lungs by means of a joint experimental and numerical work. In particular, we focus on the influence of the shear-thinning mucus mobilized by a ciliated epithelium for mucociliary clearance. The proposed robust numerical method is able to manage variations of more than 5 orders of magnitude in the shear rate and viscosity. It leads to a cartography that allows to discuss major issues on defective mucociliary clearance in cystic fibrosis. Furthermore, the computational rheological analysis based on measurements shows that cystic fibrosis shear-thinning mucus tends to aggregate in regions of lower clearance. Yet, a rarefaction of periciliary fluid has a greater impact than the mucus shear-thinning effects.
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http://dx.doi.org/10.1016/j.jbiomech.2016.12.026 | DOI Listing |
J Control Release
January 2025
Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; CHU de Brest, Service de Génétique Médicale et de Biologie de la Reproduction, F-29200 Brest, France. Electronic address:
Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping the hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, pulmonary fibrosis or lung cancer requires an enhanced understanding of the relationships between the natural physiology of the respiratory system and the pathophysiology of these conditions. This knowledge is crucial to better predict and thereby control drug deposition.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
The development of a inhaled nanodrug delivery assessment platform is crucial for advancing treatments for chronic lung diseases. Traditional in vitro models and commercial aerosol systems fail to accurately simulate the complex human respiratory patterns and mucosal barriers. To address this, we have developed the breathing mucociliary-on-a-chip (BMC) platform, which replicates mucociliary clearance and respiratory dynamics in vitro.
View Article and Find Full Text PDFPharmaceutics
December 2024
Department of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University, 28040 Madrid, Spain.
The pulmonary route for drug administration has garnered a great deal of attention in therapeutics for treating respiratory disorders. It allows for the delivery of drugs directly to the lungs and, consequently, the maintenance of high concentrations at the action site and a reduction in systemic adverse effects compared to other routes, such as oral or intravenous. Nevertheless, the pulmonary administration of drugs is challenging, as the respiratory system tries to eliminate inhaled particles, being the main responsible mucociliary escalator.
View Article and Find Full Text PDFInt J Pharm
January 2025
College of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA. Electronic address:
Intranasal drug administration offers a promising strategy for delivering combination antiretroviral therapy (cART) directly to the central nervous system to treat NeuroAIDS, leveraging the nose-to-brain route to bypass the blood-brain barrier. However, challenges such as enzymatic degradation in the nasal mucosa, low permeability, and mucociliary clearance within the nasal cavity must first be addressed to make this route feasible. To overcome these barriers, this study developed solid lipid nanoparticles (SLNs) with varying PEGylation levels (0 %, 5 %, 10 %, and 15 % w/w of PEGylated lipid), co-encapsulated with Elvitegravir (EVG) and Atazanavir (ATZ) as an integrase and protease inhibitor, respectively.
View Article and Find Full Text PDFAm J Otolaryngol
December 2024
Department of Pediatrics, Virginia Commonwealth University School of Medicine, 1000 East Broad St., Richmond, VA, USA. Electronic address:
Background: Allergic rhinitis (AR) and acute non-allergic rhinosinusitis (ARS) often present with similar symptoms. While these are generally differentiated by history and occasionally by secretion cell counts, there are few data temporally comparing these conditions.
Methods: A prospective, observational study was conducted to assess nasal mucus properties, nasal obstruction, nasal secretion cells, and health related QOL during the acute phase (Day 5) and during a later phase of illness (Day 14/28).
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