Hydrogen peroxide responsive covalent cyclodextrin framework for targeted therapy of inflammatory bowel disease

Abstract

The incidence and prevalence of inflammatory bowel disease (IBD) are steadily rising worldwide, where the pathogenesis and progression are intrinsically connected to oxidative stress and irregular high levels of reactive oxygen species. To achieve effective therapy for IBD, using hydrogen peroxide (H2O2)-activatable antioxidant prodrug (BRAP) as a linker to crosslink cyclodextrin metal-organic framework, a novel H2O2 responsive covalent cyclodextrin framework (defined as BCOF) was formulated. BCOF featured excellent ROS-responsive hydrolysis and therapeutic p-hydroxybenzyl alcohol released in a H2O2 concentration dependent manner in vitro. Furthermore, BCOF demonstrated 5 times greater retention in the inflamed colon compared to the normal colon in vivo following oral administration. Most importantly, BCOF improved the viability of RAW264.7 cells from H2O2-induced damage in vitro and alleviated the deterioration of IBD with reduced symptoms of inflammation in vivo. In conclusion, our findings suggest that BCOF deserve further consideration as a potential therapeutic nanomedicine for IBD treatment.