Bifunctional nanoparticles based on esterified hydroxypropyl β-cyclodextrin/quaternary ammonium chitosan for ulcerative colitis intervention

Developing oral nanoparticles (NPs) that combine anti-inflammatory effects with gut microbiome modulation enables an effective strategy for integrated ulcerative colitis (UC) therapy. Yet, the complex and dynamically evolving nature of the gastrointestinal milieu presents formidable challenges to the consistency and specificity of NP interventions. To address this challenge, this study designed and developed gastrointestinal microenvironment-adaptive NP via self-assembly, utilizing curcumin (Cur) for anti-inflammatory effects and anthocyanin (Cy) for microbiome regulation to achieve dual functional therapeutic outcomes. Employing the esterification strategy, hydroxypropyl-β-cyclodextrin (HPCD) was modified using citric acid (CA) and sulfonic acid (SA) to synthesize CACD (CA-modified HPCD) and SACD (SA-modified HPCD), respectively, which self-assembled in the presence of quaternary ammonium chitosan (HTCC), Cur, and Cy to yield NPs. NPs demonstrated high Cur encapsulation efficiency (EE) and encapsulation capacity (EC) across pH 2.0–7.0, highlighting their high gastrointestinal adaptability. In vivo experiments showed clear amelioration of colitis symptoms, including downregulation of pro-inflammatory cytokines and attenuation of tissue damage. HTCC-Cy-CACD-Cur NPs enriched Eubacterium siraeum_group and Prevotellaceae , HTCC-Cy-SACD-Cur NPs favored Peptococcus expansion , potentially contributing to improved immune regulation and attenuation of UC. These bifunctional NPs offer innovative UC therapy and precision nutrition interventions.