Airway mucus in pulmonary diseases: Muco-adhesive and muco-penetrating particles to overcome the airway mucus barriers.
Aerosol
Cystic fibrosis
Microrheology
Mucociliary clearance
Multiple particle tracking
Pulmonary drug delivery
Rheology
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
05 Mar 2023
05 Mar 2023
Historique:
received:
21
10
2022
revised:
26
01
2023
accepted:
27
01
2023
pmc-release:
05
03
2024
pubmed:
4
2
2023
medline:
25
2
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
Airway mucus is a complex viscoelastic gel that provides a defensive physical barrier and shields the airway epithelium by trapping inhaled foreign pathogens and facilitating their removal via mucociliary clearance (MCC). In patients with respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), non-CF bronchiectasis, and asthma, an increase in crosslinking and physical entanglement of mucin polymers as well as mucus dehydration often alters and typically reduces mucus mesh network pore size, which reduces neutrophil migration, decreases pathogen capture, sustains bacterial infection, and accelerates lung function decline. Conventional aerosol particles containing hydrophobic drugs are rapidly captured and removed by MCC. Therefore, it is critical to design aerosol delivery systems with the appropriate size and surface chemistry that can improve drug retention and absorption with the goal of increased efficacy. Biodegradable muco-adhesive particles (MAPs) and muco-penetrating particles (MPPs) have been engineered to achieve effective pulmonary delivery and extend drug residence time in the lungs. MAPs can be used to target mucus as they get trapped in airway mucus by steric obstruction and/or adhesion. MPPs avoid muco-adhesion and are designed to have a particle size smaller than the mucus network, enhancing lung retention of particles as well as transport to the respiratory epithelial layer and drug absorption. In this review, we aim to provide insight into the composition of airway mucus, rheological characteristics of airway mucus in healthy and diseased subjects, the most recent techniques to study the flow dynamics and particle diffusion in airway mucus (in particular, multiple particle tracking, MPT), and the advancements in engineering MPPs that have contributed to improved airway mucus penetration, lung distribution, and retention.
Identifiants
pubmed: 36736964
pii: S0378-5173(23)00081-9
doi: 10.1016/j.ijpharm.2023.122661
pmc: PMC9975059
mid: NIHMS1872744
pii:
doi:
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
122661Subventions
Organisme : NICHD NIH HHS
ID : R01 HD087339
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The EEG aerosol technologies described in this publication have been filed as patent applications through Virginia Commonwealth University (VCU). Michael Hindle and Worth Longest are the co-inventors, which are subject to certain rules and restrictions under VCU policy. The terms of this arrangement are being managed by VCU in accordance with its conflict of interest policies.
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