Abstract
Inflammatory bowel disease (IBD) is a chronic gut disorder that also elevates the risk of colorectal cancer (CRC). The global incidence and severity of IBD are rising, yet existing therapies often lead to severe side effects. Curcumin offers potent anti-inflammatory and chemotherapeutic properties. However, its clinical translation is hindered by rapid metabolism, as well as poor water solubility and stability, which limits its bioavailability. To address these challenges, we developed OC-S, a water-soluble and colon-targeted curcumin formulation that protects against colitis in mice. The current study advances OC-S as a dietary supplement by establishing its stability and compatibility with various commercial dietary products. Further, OC-S exhibited specific binding to inflamed colon tissue, potentially aiding in targeted drug retention at the inflammation site in colitis with diarrhea symptoms. We further investigated its efficacy in vivo and in vitro using a murine model of colitis and tumoroids from APCmin mice. OC-S significantly reduced colitis severity and pro-inflammatory cytokine expression compared with curcumin, even at very low doses (5 mg/kg/day). It also demonstrated higher anti-proliferative activity in CRC cells and colon cancer tumoroids vs. curcumin. Overall, this study demonstrated that OC-S effectively targets and retains water-soluble curcumin at the inflamed colon sites, while showing promise in addressing both colitis and colorectal cancer, which potentially paves the way for OC-S to advance into clinical development as a dietary product for both IBD and CRC.