Oral administration of nanoparticles is extremely limited due to the two processes of mucus permeation and epithelial absorption, which requires completely opposite surface properties of the nanocarriers. To tackle the contradiction, we developed a rational strategy to modify the surface of mesoporous carbon nanoparticles with chitosan concealed by a hydrophilic N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) layer. Probucol (PB) with the low poor permeability and solubility was loaded in optimal nanocarriers to realize the high loading efficacy and controlled release. The pHPMA polymer is a hydrophilic “mucus-inert” material, which could be dissociable from the surface of nanoparticles in the mucus, thus promoting their mucus permeation and causing exposure of chitosan in transepithelial transport. The swelling effect of chitosan under acidic conditions allowed regulation of PB release behavior. In conclusion, the mucus-permeable nanocarrier could effectively overcome multiple gastrointestinal absorption barriers and the oral bioavailability of PB-loaded HCMCN was 2.76-fold that of commercial preparation.

由于粘液渗透和上皮吸收这两个过程，纳米颗粒的口服给药受到极大限制，这需要纳米载体的完全相反的表面性质。为了解决该矛盾，我们开发了一种合理的策略，以被亲水性N-（2-羟丙基）甲基丙烯酰胺共聚物（pHPMA）层掩盖的壳聚糖修饰介孔碳纳米粒子的表面。将渗透性和溶解性差的丙丁酚（PB）负载在最佳的纳米载体中，以实现高负载功效和控释效果。pHPMA聚合物是亲水的“粘液惰性”材料，可以从粘液中的纳米颗粒表面解离，从而促进其粘液渗透并导致壳聚糖在上皮运输中暴露。壳聚糖在酸性条件下的溶胀作用可以调节PB的释放行为。总之，粘液可渗透的纳米载体可有效克服多种胃肠道吸收障碍，PB负载的HCMCN的口服生物利用度是市售制剂的2.76倍。