Mucus-penetrating dendritic mesoporous silica nanoparticle loading drug nanocrystal clusters to enhance permeation and intestinal absorption.

Multiple gastrointestinal barriers (mucus clearance and epithelium barrier) are the main challenges in the oral administration of nanocarriers. To achieve efficient mucus penetration and epithelial absorption, a novel strategy based on mesoporous silica nanoparticles with dendritic superstructure, hydrophilicity, and nearly neutral-charged modification was designed. The mPEG covalently grafted dendritic mesoporous silica nanoparticles (mPEG-DMSNs) had a particle size of about 200 nm and a loading capacity of up to 50% andrographolide (AG) as a nanocrystal cluster in the mesoporous structure. This dual strategy of combining with the surface topography structure and hydrophilic modification maintained a high mucus permeability and showed an increase in cell absorption. The mPEG-DMSN formulation also exhibited effective transepithelial transport and intestinal tract distribution. The pharmacokinetics study demonstrated that compared with other AG formulations, the andrographolide nanocrystals-loaded mPEG-DMSN (AG@mPEG-DMSN) exhibited much higher bioavailability. Also, AG@mPEG-DMSN could significantly improve the in vitro and in vivo anti-inflammatory efficacy of AG. In summary, mPEG-DMSN offers an interesting strategy to overcome the mucus clearance and epithelium barriers of the gastrointestinal tract.