Ionic and thermo-switchable polymer-masked mesoporous silica drug-nanocarrier: High drug loading capacity at 10 °C and fast drug release completion at 40 °C

Abstract

The preparation of the ideal smart drug-delivery systems were successfully achieved by the in situ co-polymerization of a vinyl group-functionalized mesoporous silica nanoparticle (f-MSN) with 1-butyl-3-vinyl imidazolium bromide (BVIm) and N-isopropylacrylamide (NIPAAm) monomers. The thickness of the capping copolymer layer, poly(NIPAAm-co-BVIm) (p-NIBIm), was controlled at between 2.5nm and 5nm, depending on the monomers/f-MSN ratio in the reaction solution. The finally obtained smart drug-delivery systems are named as p-MSN2.5 and p-MSN5.0 (MSNs integrated by 2.5nm and 5nm p-NIBIm layer in thickness). The key roles of the mesoporous-silica-nanoparticle (MSN) core and the p-NIBIm shell are drug-carrying (or containing) and pore-capping, respectively, and the latter has an on/off function that operates in accordance with temperature changes. According to the swelling- or shrinking-responses of the smart capping copolymer to temperature changes between 10°C and 40°C, the loading and releasing patterns of the model drug cytochrome c were studied in vitro. The developed system showed interesting performances such as a cytochrome-c-loading profile (loading capacity for 3h=26.3% and 19.8% for p-MSN2.5 and p-MSN5.0, respectively) at 10°C and a cytochrome-c-releasing profile (releasing efficiency=>95% within 3 days and 4 days for p-MSN2.5 and p-MSN5.0, respectively) at 40°C. The cytotoxicity of the drug delivery systems, p-MSN2.5 and p-MSN5.0 (in the concentration range of <0.125mg/mL without drug), for human embryonic kidney (HEK 293) cells were minimal in vitro compared with that of a blank MSN. These results may be reasonably applied in the field of specified drug delivery.