Effect of particle size and surface charge of nanoparticles in penetration through intestinal mucus barrier

Mucus is a semipermeable membrane that acts as a barrier for the transport of nanoparticles delivered through the oral route. The objective of this study was to investigate the effect of particle size and surface charge on the penetration of nanoparticles through the intestinal mucus barrier. Polystyrene fluorescent nanoparticles of varying particle sizes, including 50, 100, 200, 500, 750, 1000 nm, were utilized to study the effect of particle size on mucus penetration. Also, nanoparticles with amino and carboxylate/sulfate surface functional groups were utilized to study the effect of surface charge. A 24-well plate with transwell insert containing rabbit intestinal mucus was modeled as a diffusion cell setup to perform nanoparticle permeation studies. Results showed that particles with 50 nm diameter permeated to a significantly (p < 0.05) greater extent across mucus compared with particles of >= 200 nm size. Confocal laser scanning microscopic images showed the accumulation of particles of >= 200 nm within mucus with the progression of incubation time. In the case of particles with different surface functional groups, mucus permeation was found to be significantly (p < 0.05) greater for neutral and sulfate group particles compared with particles of amino surface. In conclusion, the most desirable particle size and surface charge for nanoparticle mucus penetration were found to be 50 nm and neutral, respectively. Graphical abstract