Design of pH-responsive sodium alginate hydrogel microspheres for targeted delivery of probiotics for the treatment of ulcerative colitis in mice.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and its pathogenesis is closely related to the dysbiosis of intestinal microbiota and the excessive activation of the immune system. Research has shown that Lactobacillus spp. can alleviate UC by enhancing intestinal barrier function and modulating immune responses. However, the primary challenge lies in ensuring the targeted release and survival of Lactobacillus spp. This research aims to develop a drug delivery system comprising Lactobacillus reuteri strain C1/5R (L.r) encapsulated in zeolitic imidazolate framework (ZIF)-67/sodium alginate (SA) hydrogel microspheres (L.r@ZIF/SA) to achieve targeted delivery of the probiotic to the colon. This study employed dihydrogenourea (taxifolin, TAX) as a pre-intervention to enrich Lactobacillus spp. in the intestinal tract of mice. SA was used as a matrix to encapsulate L. r and ZIF-67. The pH-sensitive characteristics of ZIF-67 enabled in situ crosslinking of SA in the stomach to form stable hydrogels. The hydrogels were converted into emulsion-processed microspheres with reduced particle size to facilitate gastric transit. The pH-dependent degradation of ZIF-67 in the intestine enabled the controlled release of L. r, which modulated the gut microbiota, exerted anti-inflammatory activities, and restored epithelial barrier function. This research overcomes limitations of UC in terms of low oral probiotic viability and antibiotic resistance development, offering a therapeutically effective and clinically translatable strategy for UC management.