Work

Quantifying the effects of mucociliary clearance and cilia–drug interactions on partial drug dissolution and epithelial deposition in the airway surface liquid

Year: 2026

Type: article

Abstract: Efficient pulmonary drug delivery critically depends on the complex interplay between mucus rheology, ciliary motion, and physicochemical drug properties within the airway surface liquid (ASL). In this study, a three-dimensional numerical model of a tracheal ASL segment was developed to investigate the coupled effects of mucociliary clearance (MCC), partial drug dissolution, dissolved particle size, and cilia-drug interactions on drug transport and deposition. The mucus layer was modelled as a nonlinear viscoelastic fluid, and the governing flow and mass transport equations were solved using a hybrid immersed boundary-finite difference projection method. The model simulates a partial dissolution process in which deposited microscale particles (5 µm) progressively disintegrate into nanoscale dissolved species with diameters ranging from 5 to 100 nm. Two commonly used inhaled bronchodilators - Tiotropium bromide (TIO), and Salbutamol sulfate (SAL) - and the inhaled form of the antibiotic Rifampicin (RIF), with distinct solubilities, were examined under physiologically realistic ASL conditions. Results show that MCC strongly influences drug transport and epithelial deposition, particularly for highly soluble drugs and those with larger dissolved particle sizes. For soluble compounds, MCC enhances convective transport and accelerates deposition, whereas low-solubility drugs exhibit diffusion-dominated, nearly linear deposition profiles. To quantify drug-cilia interactions, a Ciliary Attachment Ratio (CAR) was introduced. Even very small CAR values substantially reduced epithelial deposition, highlighting the need to incorporate cilia-drug adhesion in predictive models. Deposition-time analysis indicates that the diffusion coefficient is the primary determinant of absorption times, followed by drug solubility and CAR.

Source: International Journal of Pharmaceutics

DOI: 10.1016/j.ijpharm.2026.126636

Authors: MohammadHadi Sedaghat, Pinelopi Anagnostopoulou, Omid Abouali, Stavros Kassinos

Institutions: University of Cyprus, KTH Royal Institute of Technology

Language: English

Topic: Inhalation and Respiratory Drug Delivery

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650