pH-controllable release using functionalized mesoporous silica nanoparticles as an oral drug delivery system

We designed a novel oral colon-specific drug delivery system (OCDDS) using a modification of mesoporous silica nanoparticle (MSN) surfaces with pH-sensitive trimethylammonium (TA) groups through a pH-sensitive hydrazone bond. The pH-sensitive TA groups can efficiently increase the loading amounts of anionic drugs by a strong electrostatic attraction. After oral administration, the acidic pH of gastric juice can fully hydrolyze the TA–hydrazone bonds and further eliminate the positive charges of TA groups from MSN surfaces. When the hydrolyzed complexes were further delivered to the colon's pH of 7–8, a rapid and complete release of adsorbed drugs was observed. From the studies of spectroscopic characterizations, we demonstrated that the combination of pH-sensitive hydrazone–TA groups and nano-sized particles of the MSN carriers took the advantages of increasing the accessible surface areas of drug molecules and varying the charges of MSN surfaces, which can increase dissolution and release rate of hydrophobic drug molecules. In addition, a cell viability assay also indicated that no cytotoxicity of MSN–hydrazone–TA complexes was observed even with treatment in an extremely high nanoparticle concentration. Consequently, our new formulation is highly biocompatible for the OCDDS, and we can completely solve the low stability, low solubility, and low drug bioavailability in the free form of drug molecules for the design of OCDDS.