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

粘液是一种半透膜，可作为通过口服途径递送的纳米颗粒运输的屏障。这项研究的目的是研究粒径和表面电荷对纳米颗粒通过肠粘液屏障的渗透的影响。利用包括50、100、200、500、750、1000 nm在内的各种粒径的聚苯乙烯荧光纳米颗粒来研究粒径对粘液渗透的影响。同样，具有氨基和羧酸盐/硫酸盐表面官能团的纳米颗粒被用于研究表面电荷的影响。将具有包含兔肠粘液的transwell插入物的24孔板建模为扩散池设置，以进行纳米颗粒渗透研究。结果表明，直径为50 nm的颗粒渗透到 与≥200 nm大小的颗粒相比，在整个粘液中的分布范围更大（p <0.05）。共聚焦激光扫描显微图像显示，随着培养时间的延长，粘液中≥200 nm的颗粒积聚。对于具有不同表面官能团的 颗粒，与氨基表面的颗粒相比，中性和硫酸盐基团的颗粒的粘液渗透性明显更高（p <0.05）。总之，发现用于纳米颗粒粘液渗透的最理想的粒度和表面电荷分别为50 nm和中性。

图形概要