In situ delivered chitosan-encapsulated hydrogen microbubbles for inflammatory bowel disease therapy by scavenging oxidative stress

Chitosan-encapsulated hydrogen microbubbles (CS@H 2 ) were developed for enema-based delivery, enabling sustained H 2 release directly to the inflamed intestines. Based on this strategy, CS@H 2 showed significant anti-inflammation efficacy in IBD by mitigating oxidative stress. • CS@H 2 enabled in situ hydrogen delivery to inflammation sites, ensuring sufficient therapeutic concentrations. • CS@H 2 showed significant anti-inflammation efficacy in IBD without additional medications. • CS@H 2 efficiently scavenged intracellular ROS and mitigated oxidative stress in the IBD mouse model. The development of effective therapeutic drugs with minimal side effects for inflammatory bowel disease (IBD) management remains a long-term challenge. Hydrogen molecule (H 2 ) has emerged as a promising, broad-spectrum anti-inflammatory agent with high biosafety. However, its clinical application is constrained by poor bioavailability due to rapid degradation and uncontrolled diffusibility during oral or systemic administration, resulting in inadequate concentrations at target sites. Herein, we developed chitosan-encapsulated hydrogen microbubbles (CS@H 2 ) for enema-based delivery, enabling sustained H 2 release directly to the inflamed intestines for IBD therapy. The CS@H 2 system efficaciously maintained stable hydrogen concentrations and exhibited a highly efficient capacity for neutralizing intracellular reactive oxygen species (ROS). In the mice model of dextran sulfate sodium (DSS)-induced IBD, enema administration of CS@H 2 significantly alleviated inflammation, restoring colon length, body weight, and disease activity to near-normal levels. Mechanistically, the therapeutic effects of CS@H 2 were attributed to its ability to ameliorate inflammation by scavenging oxidative stress. These findings highlight the potential of enema-administered hydrogen-based therapies for restoring intestinal homeostasis, offering a safe and effective approach to IBD treatment.