Natural chlorophyll‑sodium alginate oral hydrogel for robust treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disorder that may lead to debilitating symptoms and serious complications such as toxic megacolon, intestinal perforation, and colon cancer. Conventional oral therapies are often limited by poor bioavailability and significant adverse effects. Herein, we developed an oral hydrogel for treatment of UC by electrostatic and hydrogen-bonding interactions of chlorophyll (Chl) and sodium alginate (SA) for the first time. The as-prepared Chl-SA hydrogel exhibited excellent biocompatibility and pH-responsive properties. In vitro assays showed that it reduced TNF-α (271.51 pg/mL compared with 863.4 pg/mL in the LPS group), increased IL-10 (321.53 pg/mL compared with 91.66 pg/mL in the LPS group), and achieved 70% DPPH radical scavenging, confirming its potent anti-inflammatory and antioxidant activities. It exhibited robust therapeutic effects in a DSS-induced colitis mouse model after seven days of treatment, including ameliorating intestinal inflammation and restoring barrier integrity. These effects were achieved by mitigating oxidative stress, promoting mucosal healing and the expression of ZO-1 and occludin-1, as well as rebalancing the gut microbiota and restoring its richness and diversity. Importantly, given that hydrogels are generally known to offer advantages for patients with dysphagia over traditional oral formulations, the present study suggests that the Chl-SA hydrogel can offer therapeutic potential as a suitable oral dosage form for UC.