Redox-sensitive hydrogel based on hyaluronic acid with selenocystamine cross-linking for the delivery of Limosilactobacillus reuteri in a DSS-induced colitis mouse model

Disrupted gut microbiota homeostasis is an important cause of inflammatory colitis. Studies have shown that effective supplementation with probiotics can maintain microbial homeostasis and alleviate colitis. Here, to increase the viability of probiotics in the harsh gastrointestinal environments and enable targeted delivery, a redox-sensitive selenium hyaluronic acid (HA-Se) hydrogel encapsulating probiotics was developed. HA was modified with selenocystamine dihydrochloride and crosslinked by an amide reaction to generate a redox-sensitive hydrogel with stable mechanical properties, a low hemolysis rate and satisfactory biocompatibility. The HA-Se hydrogel exhibited suitable sensitivity to 10 mM GSH or 100 μM H₂O₂. The encapsulation of Limosilactobacillus reuteri (LR) in the HA-Se hydrogel (HA-Se-LR) significantly increased the survival rate of the probiotics in simulated gastric and intestinal fluid. HA-Se-LR administration increased the survival rate of mice with dextran sulfate sodium (DSS)-induced colitis, significantly alleviated oxidative stress and inflammation, and increased the effect of LR on microbiota α diversity. These results indicate that the HA-Se hydrogel constructed in this study can be used as a delivery platform to treat colitis, expanding the targeted applications of the natural polymer HA in disease treatment and the administration of probiotics as drugs to alleviate disease symptoms.

Hyaluronic acid; Hydrogel; Inflammatory bowel disease; Limosilactobacillus reuteri; Redox sensitivity.