A Model for the Transient Subdiffusive Behavior of Particles in Mucus.

In this study we have applied a model to explain the reported subdiffusion of particles in mucus, based on the measured mean squared displacements (MSD). The model considers Brownian diffusion of particles in a confined geometry, made from permeable membranes. The applied model predicts a normal diffusive behavior at very short and long time lags, as observed in several experiments. In between these timescales, we find that the "subdiffusive" regime is only a transient effect, MSD∝τα,α<1. The only parameters in the model are the diffusion-coefficients at the limits of very short and long times, and the distance between the permeable membranes L. Our numerical results are in agreement with published experimental data for realistic assumptions of these parameters. Finally, we show that only particles with a diameter less than 40 nm are able to pass through a mucus layer by passive Brownian motion.

Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus.

Aim of this study was to investigate the similarities and differences at macro- and microscale in the viscoelastic properties of mucus that covers the epithelia of the intestinal and respiratory tract. Natural mucus was collected from pulmonary and intestinal regions of healthy pigs. Macro-rheological investigations were carried out through conventional plate-plate rheometry. Microrheology was investigated using optical tweezers. Our data revealed significant differences both in macro- and micro-rheological properties between respiratory and intestinal mucus.

Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge--an ex vivo and in silico approach.

The fate of inhaled particles after deposition onto the pulmonary mucosa is far from being solved, in particular with respect to mucociliary clearance and mucus penetration. Due to the fact that these phenomena govern pulmonary residence time and thus bioavailability, they are highly relevant for any kind of controlled release formulation delivered via that route. This study applies ex vivo and in silico approaches to investigate the dependency of muciliary clearance of micro-, submicrometer and nanoparticles on size, shape, charge and surface chemistry of such particles. In addition, measurement of mucociliary clearance of different particles also provided information about their penetration into mucus. Surprisingly, no significant differences in mucociliary clearance could be found for any type of particle under investigation. As revealed by computational modeling, particle penetration into the mucus gel layer was negligible at least within the time frame allowed by horizontal mucus transport. These data suggest that the observed lack of difference in mucociliary clearance is caused by the lack of immediate penetration of deposited aerosol particles through the mucus blanket.