Oral colon-targeted micro-nano formulation engineered in microfluid for synergistic therapy of inflammatory bowel disease.

The management of inflammatory bowel disease (IBD) continues to pose a substantial clinical obstacle, owing to the intricate nature of its pathophysiology. Targeted micro/nano drug delivery systems, which can exploit the synergistic effects of multiple components, represent a promising therapeutic strategy. In this study, we developed a colon-targeted co-delivery system based on hydrogel microspheres (CCB@HMs) using droplet microfluidics, serving as a versatile micro/nano platform for IBD therapy. This system enables the targeted delivery of budesonide (BDS) while leveraging curcumin (Cur) and inulin as both drug carriers and antioxidants, thereby compensating for the limited reactive oxygen species (ROS)-scavenging capacity of BDS and achieving synergistic therapeutic effects. In vitro and in vivo evaluations demonstrated that CCB@HMs efficiently deliver drugs to inflamed colonic tissues, providing prolonged retention and sustained release. The microspheres effectively scavenge ROS, alleviate oxidative stress, modulate intestinal immunity, repair the epithelial barrier, and restore gut homeostasis. Collectively, these results confirm the synergistic therapeutic effects of CCB@HMs in a murine colitis model, positioning them as a promising targeted and multifunctional oral delivery strategy for IBD.