Development of photo and pH dual crosslinked coumarin-containing chitosan nanoparticles for controlled drug release

Abstract

A new strategy has been developed to the fabrication of chitosan nanoparticles as anticancer drug nanocarriers with ultraviolet-responsive coumarin derivatives and pH-responsive imine groups. For this purpose 8-formyl-7-hydroxy-4-methylcoumarin (8-FHMC) was initially synthesized as novel and dual crosslinking agent in order to produce coumarin-containing chitosan nanoparticles via oil-in-water nanoemulsion system. The structure of the resultant compounds and nanoparticles were confirmed by means of 1H NMR, FT-IR, UV–vis spectroscopy and XRD. The morphology and size distribution of the coumarin-containing chitosan nanoparticles was also characterized using SEM, AFM and DLS. The drug-loaded coumarin-containing chitosan nanoparticles were stable at physiological conditions, and can also be disassociated by the cleavage of imine linkages in the crosslinking segments under acidic condition. Compared to non-photo-crosslinked chitosan nanoparticles, photo-crosslinked chitosan nanoparticles displayed controllable and slower release. Thus, we have showed that chitosan nanoparticles crosslinked by coumarin with photo- and pH-responsive properties is a promising and novel drug carrier for designing intelligent drug delivery systems.