Nanoparticle Diffusion in Respiratory Mucus Influenced by Mucociliary Clearance: A Review of Mathematical Modeling

Inhalation and deposition of particles in human airways have attracted considerable attention due to importance of particulate pollutants, transmission of infectious diseases, and therapeutic delivery of drugs at targeted areas. We summarize current state-of-the art research in particle deposition on airway surface liquid (ASL) influenced by mucociliary clearance (MCC) by identifying areas that need further investigation. We aim to review focus on governing and constitutive equations describing MCC geometry followed by description of mathematical modeling of ciliary forces, mucus rheology properties, and numerical approaches to solve modified time-dependent Navier-Stokes equations. We also review mathematical modeling of particle deposition in ASL influenced by MCC, particle transport in ASL in terms of Eulerian and Lagrangian approaches, and discuss the corresponding mass transport issues in this layer. Whenever required, numerical predictions are contrasted with the pertinent experimental data. Results indicate that mean mucus and periciliary liquid velocities are strongly influenced by mucus rheological characteristics as well as ciliary abnormalities. However, most of the currently available literature on mucus fiber spacing, ciliary beat frequency, and particle surface chemistry is based on particle deposition on ASL by considering a fixed value of ASL velocity. The effects of real ASL flow regimes on particle deposition in this layer are limited. In addition, no other study is available on modeling nonhomogeneous and viscoelastic characteristics of mucus layer on ASL drug delivery. Simplification of assumptions on governing equations of drug delivery in ASL influenced by MCC leads to imposing some limitations on numerical results.