Transport and fate of inhaled particles after deposition onto the airway surface liquid: A 3D numerical study

Abstract

In this paper, a numerical investigation is carried out to provide insights into the fate of inhaled aerosols after their deposition on the lung lining fluid in both healthy and diseased states. Pulmonary drug delivery is a well-known non-invasive route of administration compared to intravenous delivery. Aerosol particles are formulated and used as drug carriers, which are then sent to the airways using aerosol drug delivery devices. This approach is useful for site-specific treatment of lung diseases, treatment of central nervous system (CNS) disorders and a variety of other diseases. Bioavailability of the inhaled therapeutic particles after landing on the airway lining fluid can be significantly altered by the lung muco-ciliary clearance, a process through which hairlike structures known as cilia beat in a harmonised manner and induce the mucus in the proximal direction, leading to an effective clearance of the foreign inhaled particles entrapped by this sticky layer from the airways. Here, we set up a 3D computational model of ciliary arrays interacting with periciliary liquid film (i.e. confined between the epithelium and mucus layer) and a detailed analysis is conducted to better understand the fate of drug nanoparticles that are able to penetrate the mucus. Consistent with clinical findings, we find that the actions of cilia result in a low rate of drug retention and absorption by the pulmonary tissues in healthy lungs. However, under conditions associated with abnormal ciliary beats, the retention time of particles is notably increased at the site of release. Nonetheless, the results associated with some of the ciliary impairments reveal that deposition of drug aerosols on the ciliated cells may still be a significant challenge. These findings have potentially important implications on the modification of therapeutic drug particles to achieve a higher absorption rate.