Insights into transport in mucus barrier: Exploring particle penetration through the intestinal mucus layer

Abstract

Nearly all pharmaceuticals and nutrients must cross numerous barriers to gain access and be eliminated from the body. The gastrointestinal mucosa, comprised of specialized epithelial cells layered with mucus, is among the most critical of these barriers. With its intricate structure, this mucus layer facilitates nutrient transport and impedes the transit of toxins and bacteria. The permeability of this mucus layer is key in determining the temporal availability and concentration of various compounds. Numerous methods for enhancing the permeability of select particles through this layer have been examined, employing diverse techniques to quantify the impact of these alterations. However, studies exploring mucus permeability have largely overlooked the potential effect of fluid flow on the mucus layer. In this research, we apply numerical methods to investigate the penetration of particles and drugs through the mucus layer towards the intestinal epithelium, comparing the benefits and distinctions of these methods. To simulate hydrodynamic effects within the mucus layer, we model intestinal mucus as a Herschel Bulkley fluid, solving the Navier-Stokes equations to simulate fluid flow. These equations are integrated with mass transfer equations to emulate particle penetration through the mucus layer. Our work utilized two different scenarios to simulate the penetration of Brilliant Blue FCF (BFC) into the mucus layer. In the first scenario, molecular diffusion is the sole mechanism responsible for mass transfer. In the second scenario, we also consider convection as an auxiliary mechanism for BFC penetration. By comparing our simulation outcomes with experimental observations, we demonstrate the necessity of incorporating the convection term to accurately mirror experimental findings. Moreover, we analyzed the effect of varying the diffusion coefficient and viscosity on penetration. The findings revealed that both parameters significantly influence BFC penetration. We also assessed the concentration of drug samples and particles of varying sizes and surface coatings at the epithelial layer. The simulation-based methodology developed in this study shows that internal fluid flow within the mucus layer can profoundly impact particle transport, necessitating the consideration of the convection mechanism for mass transfer in both numerical simulations and penetration analyses.