Butyrate-Conjugated Poly(vinyl alcohol) Nanoparticles in an Inulin Hydrogel for Colon-Targeted Drug Delivery in Colitis

The development of oral drug delivery systems with colon-targeted release and high biocompatibility is of critical importance for the treatment of ulcerative colitis (UC), considering the chronic nature of the disease and the genetic susceptibility of patients. Herein, we report a composite delivery system (UA@PB/Gel) based on Generally Recognized As Safe (GRAS) materials, poly(vinyl alcohol) (PVA) and inulin, designed for colon-specific delivery of ursolic acid (UA). In this system, butyrate-conjugated PVA nanoparticles efficiently encapsulate UA and respond to colonic esterase, enabling the localized release of both UA and butyrate. Embedding these nanoparticles within an inulin hydrogel further enhances colonic retention and provides a sustained release. The composite system demonstrates efficient colon-targeting delivery, prolonged retention, and potent anti-inflammatory effects in vitro and in vivo. In a dextran sulfate sodium-induced colitis mouse model, UA@PB/Gel effectively alleviates colonic inflammation, restores epithelial barrier integrity, reduces proinflammatory cytokine expression, and modulates gut short-chain fatty acid levels, with minimal systemic toxicity. These results highlight the potential of the GRAS materials-based nanoparticle-hydrogel composite as a safe and effective therapeutic platform for UC.