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Publication

Computer modeling of aerosol diffusion through lung mucosa

Bartlett, Blake
Feng, Yu
Fromen, Catherine A.
Abstract
Diseases of the lung are some of the most common and deadly in the world, accounting for 4 of the top 10 global causes of death according to the World Health Organization. Existing treatments, if any exist, tend to be extremely rigorous, invasive, and time-consuming. Further, due to the poor bioavailability of drugs traditionally administered orally or through injection, these treatments are not very effective. Technology is emerging that allows an aerosolized drug dosage to be delivered directly to the diseased area; however, the mucus layer separating the airways from the tissue (and the blood) remains a barrier to this method. In order to combat this, this research has constructed a physics-based computer model of the mucosal interface between the airways and the lung tissues, providing a much-needed insight into how a vaccine, antibiotic, or other drug must behave to effectively reach the target tissue in various lung regions.
The lung has a phenomenal system called the mucociliary clearance mechanism in place to clear foreign particles (including cigarette ash, dust, and bacteria), prevent infection, and keep the lungs healthy. A layer of mucus on the surface of the inner lung is constantly pushed upward towards the throat by a bed of cilia, and most particles that impact on the mucus are cleared from the lungs quickly and without incident. However, when it fails to prevent a disease from being contracted, it remains a barrier to drug delivery, as those particles must cross the same thick mucus layer.
The model uses COMSOL Multiphysics software to visualize the mucosa as a cross-section. Data from the literature is used to determine details like dimensions, velocity, and viscosity. The mucus layer moves upwards towards the throat in laminar flow, imitating the mucociliary effect, and the underlying periciliary layer has no net movement due to the regular beating of the cilia that move the mucus. The "drug" enters from the airway side and moves through the fluid by convection. Given these inputs, the model outputs an image showing how much, if any, of the administered particle diffuses through the mucosa and reaches the tissue. The model is extremely customizable, easily modified to simulate other drugs or any other particle so long as some properties are known. Variables have been specifically parametrized to find more complex relationships, like effective diffusivity, from an input of more readily available information, like particle radius. Lung conditions can also be quickly altered to meet the needs of the user (for example, the mucus layer is much thinner in the alveolar region, and the mucus of cystic fibrosis patients is much denser than average). Thus, the model can quickly provide greater insight into the efficacy of new lung treatments.
Date
2020-04-24