A biodegradable pH and glutathione dual-triggered drug delivery system based on mesoporous silica, carboxymethyl chitosan and oxidized pullulan

A simple and smart drug controlled delivery system is developed in this work. Biodegradable mesoporous silica nanoparticles (BMSN) were first synthesized by introducing disulfide during the synthesis of mesoporous silica nanoparticles (MSN), which were used for the loading of methotrexate (MTX), an anti-cancer drug. The MTX loaded BMSN (BMSN-MTX) was then encapsulated in the hydrogels of carboxymethyl chitosan (CMCS)/oxidized pullulan (OPL) generated through Schiff base reaction. The acylhydrazone bonds (-N=CH-) between CMCS and OPL are prone to be hydrolyzed in acidic medium while the disulfide linkage (-S-S-) in the BMSN can be cleaved in the presence of glutathione (GSH), and thus the delivery of MTX from the BMSN-MTX-gel can be triggered by both pH and GSH. The results of release kinetics reveal that the delivery of MTX from the biodegradable hydrogels is controlled by Higuchi model. Finally, good biocompatibility and pronounced cytotoxicity of the developed BMSN-MTX-gel are confirmed by cytotoxicity test.