A pH-sensitive dual-encapsulating delivery system: Chitosan-alginate hydrogels trapping glycyrrhizic acid/curcumin micelles for synergistic ulcerative colitis

Ulcerative colitis is an inflammatory bowel disease characterized by diffuse inflammation of the colonic and rectal mucosa. Although Curcumin (Cur) has demonstrated multiple benefits for the host, its poor water solubility and rapid metabolism result in extremely low bioavailability. Therefore, a targeted delivery strategy is needed to transport Cur to the colon and allow its accumulation at disease sites. In this study, a novel pH-responsive oral hydrogel delivery system was developed. Cur/GA nanomicelles were first prepared by self-assembling curcumin (Cur) with the amphiphilic glycyrrhizic acid (GA). These nanomicelles were then loaded into gel beads composed of a crosslinked sodium alginate (SA) and chitosan (CS) network, thus enabling colon-targeted release. The hot air-dried hydrogel beads exhibited an average moisture content of 7.97 %, a particle size of 0.73 mm, and a high drug loading capacity of 15.3 %. Furthermore, microscopic analysis confirmed their spherical morphology and good fluidity. The formulation demonstrated excellent colon-targeting properties, with negligible drug release under acidic conditions but sustained release at pH 6.8/7.4, achieving a cumulative rate exceeding 80 %. In vivo evaluations against ulcerative colitis revealed that the Cur/GA-micelle-gel-beads were significantly more effective than Cur/GA-micelles alone in alleviating DSS-induced symptoms, mitigating colon shortening, and suppressing pro-inflammatory cytokines (IL-6, IL-1β, TNF-α). Specifically, the therapeutic mechanism was primarily attributed to the regulation of macrophage M1/M2 polarization. In conclusion, our findings indicate that Cur/GA-micelle-gel-beads possess favorable colon-targeting properties and anti-UC efficacy, offering a novel strategy for the targeted treatment of UC.