Thermo-responsive methylcellulose/hyaluronic acid–mesalamine hydrogel in targeted drug delivery for ulcerative colitis

Abstract

Current treatments for ulcerative colitis (UC), including mesalamine (Me) enemas, face limitations such as poor colonic retention, systemic side effects, and suboptimal patient compliance. To address these challenges, this study developed a thermo-responsive hydrogel combining hyaluronic acid–mesalamine (HA–Me) conjugates with methylcellulose (MC), providing a targeted and sustained drug delivery platform for UC treatment. HA–Me conjugates were synthesized via a nucleophilic addition–elimination reaction, with FT-IR and ¹H-NMR confirming successful conjugation and a grafting ratio of 12.45%. Rheological analysis revealed a lower critical solution temperature (LCST) of 36.7–37.7 °C, ensuring gelation at body temperature when the MC concentration was 5–7 wt%. The optimized hydrogel exhibits intestinal retention properties, thereby improving drug bioavailability. The results confirmed that this hydrogel not only improved drug release time but also provided a protective barrier for inflamed wounds, facilitating wound healing, reducing the risk of reinfection, and improving medical compliance. Its mucoadhesive properties further supported effective drug delivery and localized therapeutic effects. This study highlights the potential of the MC/HA–Me hydrogel as a platform for overcoming the limitations of conventional UC treatments, offering opportunities for tailored therapeutic applications and future clinical development.