Antioxidant-Targeting Synergistic Probiotic Delivery System with Improved Probiotics Viability and Intestinal Retention for Ulcerative Colitis Therapy

Oral probiotics are a multitarget regulatory strategy for treating ulcerative colitis (UC), but their viability is mainly affected by gastric acid and reactive oxygen species (ROS). Herein, a pH and ROS dual-responsive alginate-based hydrogel facilitating the delivery of epigallocatechin gallate (EGCG)-Mn nanoparticle-modified Lacticaseibacillus rhamnosus GG (LGG@EGCG-Mn) to the colon is constructed to treat UC. EGCG-Mn layer enhances LGG’s oxidative stress resistance by 6.28-fold. The dual-responsive alginate/thioketal hydrogel (SA-tK-Ca 2+ ) protects LGG@EGCG-Mn from gastric acid with a 71.6% survival rate and releases it at colonic lesions, resulting in improved LGG@EGCG-Mn colon retention. In vivo, LGG@EGCG-Mn@SA-tK-Ca 2+ effectively prevents and treats UC by increasing the expression of ZO-1 and Occludin to restore the intestinal barrier, mitigating colon inflammation, maintaining intestinal homeostasis, and facilitating the synthesis of short-chain fatty acids. This study overcomes the challenges of probiotic delivery across the barriers of harsh gastric pH and intestinal ROS, offering a more effective probiotic therapy for UC.