Oral Administration of Metal-Phenolic-Inspired Curcumin Self-Assemblies for Colitis Alleviation

Natural bioactive compounds hold promise for ulcerative colitis (UC) but are limited by their poor bioavailability and efficacy. Herein, we propose an interdisciplinary strategy termed “natural bioactive compound-nanotechnology-multipronged modulation” to develop an oral, biocompatible nanoparticle system (CTAl NPs) via a self-assembly strategy. Curcumin (Cur) was successfully encapsulated within a tannic acid (TA) and Al3+ coordination network through hydrogen bonding, π–π stacking, and coordination interactions. The resulting CTAl NPs confer therapeutic benefits through three synergistic mechanisms, including potent anti-inflammatory and antioxidant activities, restoration of immune homeostasis, and reinforcement of the intestinal barrier. These effects stem from the complementary functionalities of each component: TA–Al3+ coordination confers mucosal adhesion and immune modulation, while Cur contributes intrinsic anti-inflammatory activity. This tricomponent system demonstrates enhanced efficacy, offering a facile, safe, and efficient approach for UC management and broader insight into treating inflammation-related disorders.