Models using native tracheobronchial mucus in the context of pulmonary drug delivery research: Composition, structure and barrier properties

Mucus covers all wet epithelia and acts as a protective barrier. In the airways of the lungs, the viscoelastic mucus meshwork entraps and clears inhaled materials and efficiently removes them by mucociliary escalation. In addition to physical and chemical interaction mechanisms, the role of macromolecular glycoproteins (mucins) and antimicrobial constituents in innate immune defense are receiving increasing attention. Collectively, mucus displays a major barrier for inhaled aerosols, also including therapeutics. This review discusses the origin and composition of tracheobronchial mucus in relation to its (barrier) function, as well as some pathophysiological changes in the context of pulmonary diseases. Mucus models that contemplate key features such as elastic-dominant rheology, composition, filtering mechanisms and microbial interactions are critically reviewed in the context of health and disease considering different collection methods of native human pulmonary mucus. Finally, the prerequisites towards a standardization of mucus models in a regulatory context and their role in drug delivery research are addressed.