Barrier properties of gastrointestinal mucus to nanoparticle transport

Gastrointestinal mucus, a complex network of highly branched glycoproteins and macromolecules, is the first barrier through which orally delivered drug and gene vectors must traverse. The diffusion of such vectors can be restricted by the high adhesivity and viscoelasticity of mucus. In this investigation, the barrier properties of gastrointestinal mucus to particle transport were explored using real-time multiple particle tracking. The influence of surface chemistry on particle transport rates was examined using amine-, carboxylate-, and sulfate-modified polystyrene nanoparticles. A strong dependence of particle mobility in gastrointestinal mucus on surface charge was observed, with anionic particles diffusing 20-30 times faster than cationic particles. Comparison of diffusion coefficients calculated for gastrointestinal mucus with significantly varying values previously reported in the literature for other mucus sources, including cervicovaginal mucus and cystic fibrosis sputum, highlight the dependence of mucus barrier properties on the anatomical source. A significant degree of transport rate heterogeneity was also observed in native gastrointestinal mucus, suggesting a highly heterogeneous distribution of pore sizes. Furthermore, the suitability of purified mucin as a model system for transport studies was assessed by comparing particle transport rates between native intestinal mucus and purified porcine gastric mucin. Particle transport rates were approximately threefold lower in native mucus compared to purified mucin for anionic particles, yet comparable for cationic particles. Differences between barrier properties of the purified mucin preparation and native mucus depended on specific carrier properties, indicating that the purified mucin preparation does not provide an accurate model system for native mucus.