The Effect of Cilia and the Mucociliary Clearance on Successful Drug Delivery

Abstract

Nasal mucociliary clearance is one of the most important factors affecting nasal delivery of drugs and vaccines. This is also the most important physiological defense mechanism inside the nasal cavity. It removes inhaled (and delivered) particles, microbes and substances trapped in the mucus. Almost all inhaled particles are trapped in the mucus carpet and transported with a rate of 8-10 mm/h toward the pharynx. This transport is conducted by the ciliated cells, which contain about 100-250 motile cellular appendages called cilia, 0.3 µm wide and 5 µm in length that beat about 1000 times every minute or 12-15 Hz. For efficient mucociliary clearance, the interaction between the cilia and the nasal mucus needs to be well structured, where the mucus layer is a tri-layer: an upper gel layer that floats on the lower, more aqueous solution, called the periciliary liquid layer and a third layer of surfactants between these two main layers. Pharmacokinetic calculations of the mucociliary clearance show that this mechanism may account for a substantial difference in bioavailability following nasal delivery. If the formulation irritates the nasal mucosa, this mechanism will cause the irritant to be rapidly diluted, followed by increased clearance, and swallowed. The result is a much shorter duration inside the nasal cavity and therefore less nasal bioavailability.

Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model

“…MCC disruption is the consequence of perturbation of a highly complex, multi-component system: such as cilia blockage or desynchronization, modification of the periciliary fluid layer and change of the viscoelasticity of the mucus, etc. (Gizurarson, 2015). While the precise reason of MCC dysfunction caused by each type of virus is not known, it is clearly related to the cell tropism of the different respiratory viruses used in this study (Dijkman et al, 2013;Essaidi-Laziosi et al, 2017).…”

Preparation and Evaluation of PEGylated Poly-L-ornithine Complex as a Novel Absorption Enhancer

“…There are two clearance mechanisms in the nasal cavity: mucociliary clearance by cilia and physical clearance via the structure of the nasal cavity. 3,10,11) The substances trapped in the nasal mucus are transferred to the pharynx by these mechanisms, and drugs and absorption enhancers administered in the nasal cavity are removed from the absorption area. Polycationic absorption enhancers do not have mucoadhesive/retentive properties.…”

Stem cell-based Lung-on-Chips: The best of both worlds?

“…The relative role of these mechanisms in drug absorption varies depending on airway region. For example, the conducting airways (nasal cavity, sinuses, nasopharynx, oropharynx, larynx, trachea, bronchi, and bronchioles) are lined by ciliated cells and mucus-secreting cells, which together enable the mucociliary clearance of about 90% of inhaled particles, greatly reducing bioavailability of drug compounds [266]. In the respiratory regions, on the other hand, which comprise about 95% of the total surface area and consist of respiratory bronchioles, alveolar ducts, and alveolar sacs, drug bioavailability is limited by absorption, transport across the pulmonary air-blood barrier, and metabolic and macrophage clearance [267].…”