Succinylated casein functionalized mesoporous silica nanoplatforms to overcome multiple gastrointestinal barriers

Oral delivery of nanocarriers is exceedingly limited owing to the two speed-limited processes of epithelial absorption and mucus permeation, which demands totally opposite surface characters of nanoparticles . In order to address this contradiction, we proposed a reasonable idea about functionalizing the surface of mesoporous silica with positively charged amino groups and hydrophilic succinylated casein (SCN) polymer. Mesoporous silica nanoparticles doped with quantum dots (QMSN) with an average particle size at 160 nm were employed as the nanocarriers. Paclitaxel (PTX) with poor solubility and permeability was loaded in the nanoplatforms in a non-crystalline state to realize a relatively high drug loading efficacy of 11.9% and controlled release property. The coated SCN can hinder the premature release in gastric environment, and be specifically detachable in intestine to accelerate PTX release under the existence of trypsin, promote the mucus permeation and result in exposure of amino groups after degradation to realize efficient transepithelial transport. Compared with amino modified QMSN, QMSN-SCN showed increased intestinal uptake in vivo . Toxicity studies showed the both QMSN and QMSN-SCN had the excellent biosecurity for in vivo application. In summary, successive and easy functionalization of amino groups and SCN polymers on the surface of QMSN provide a promising strategy to conquer the multiple gastrointestinal barriers.