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

• Fabricated a realistic mouth–throat replica coated with artificial mucus (BZ365). • Applied 60-µm (oropharynx) and 20-µm (trachea) mucus layers in experiments and CFD. • Assessed effects of reduced mucosal wettability (22.5–60° contact angle) on pMDI deposition. • Overall deposition increased from 64.8% to 73.5% as the contact angle increased. • Pharyngeal deposition showed the largest rise, from 34.4% to 42.9%. 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.