Dual-crosslinked polysaccharide microspheres via glycated collagen and sodium alginate/chitosan for intestine targeted delivery of curcumin in ulcerative colitis treatment.

Polysaccharide-based hydrogel microspheres have demonstrated considerable potential for functional factors intestinal-targeted delivery and ulcerative colitis (UC) treatment. However, single-polysaccharide systems often struggle to achieve both stable loading and controlled release of functional factors. In this study, protein-polysaccharide composite microspheres were developed using a dual-crosslinking strategy. Initially, curcumin (Cur) was encapsulated within Andrias davidianus collagen (ADC) or its xylose glycated form (ADCXy) to form ADC/ADCXy-Cur complexes. These complexes were then crosslinked with sodium alginate (SA) and chelated with Ca2+ ions to construct a primary hydrogel network (ADC/ADCXy-Cur-SA). Finally, the cationic polysaccharide chitosan (CS) with colon enzymolysis targeting, mucosal adhesion and pH responsive controlled release characteristics was incorporated with ADC/ADCXy-Cur-SA to form a double cross-linked multifunctional hydrogel microsphere (ADC/ADCXy-Cur-SA-CS). Compared with ADC-Cur-SA-CS, the ADCXy-Cur-SA-CS exhibited enhanced cellular antioxidant and anti-inflammatory activity, maintained high stability in simulated gastric conditions, and enabled controlled Cur release in colonic pH environment. In vivo experiments have shown that ADCXy-Cur-SA-CS alleviated UC based on the "one stone, four birds" strategy of antioxidant, anti-inflammatory, repairing the colon mucosal barrier, and regulating the gut microbiota. This study provides an important technical and theoretical foundation for the development of multifunctional polysaccharide-based hydrogel delivery systems.