Mucoadhesion-controlled deposition and impaction dynamics of inhaled drugs in artificial mucus-coated airways: a coupled experimental–computational study

Optimizing pulmonary drug delivery requires a detailed understanding of aerosol-mucus interactions, particularly under pathological conditions such as chronic obstructive pulmonary disease (COPD), where mucus composition, rheology, and surface properties are markedly altered. This study investigated how modulating the drug-mucus contact angle-a surrogate for mucosal wettability-affects deposition outcomes in pressurized metered-dose inhalers (pMDIs). A realistic mouth-throat (MT) model was fabricated and coated with artificial pulmonary mucus, then experimentally characterized to establish a baseline contact angle of 22.5°. This baseline value was implemented in the numerical model, which was validated against in vitro Next Generation Impactor (NGI) data and subsequently extended to simulate contact angles of 40° and 60°, representing reduced wettability scenarios typical of severe COPD. Our findings showed that disease-altered wettability conditions (θ = 60°) increased overall drug deposition by approximately 13.4 % compared with the healthy airway condition (θ = 22.5°), underscoring the adhesive contribution to droplet retention. Simulations further revealed that oropharyngeal deposition is highly sensitive to mucus wettability: lower interfacial tension promoted complete spreading and mucosal absorption, whereas higher interfacial tension led to droplet rebound, limited transfer, and downstream re-entrainment. Collectively, these findings provide mechanistic insight into how controlling drug-mucus interfacial characteristics can improve aerosol delivery in disease-compromised airways.