Formation of Curdlan–Curcumin helically structured nanogels for targeted anti-inflammatory nanotherapy

Curdlan possesses intrinsic macrophage-binding ability, making it a promising platform for targeted drug delivery. However, constructing curdlan–drug complexes with well-defined structures and predictable biological functions remains challenging due to difficulties in controlling curdlan conformations. In this study, we developed a self-assembling nanogel system composed of low-molecular-weight curdlan (LCD) and curcumin. Molecular dynamics simulations and circular dichroism analyses revealed two interaction modes—curcumin bound to the triple-helix surface and encapsulated within the single-helix core—which together drive the spontaneous formation of stable LCD–curcumin nanogels. FTIR, DSC, SEM, and DLS characterizations confirmed their structural integrity and preserved helical organization. Cell-based evaluations showed that the nanogels mitigated curcumin cytotoxicity, enhanced its anti-inflammatory activity, and promoted uptake by RAW264.7 macrophages. Studies in a mouse model of ulcerative colitis demonstrated improved curcumin bioavailability, stronger therapeutic effects, and good systemic safety. Overall, these results indicate that LCD–curcumin nanogels possess controlled helical structures and potent anti-inflammatory properties, highlighting their potential as an effective nanomedicine for inflammatory disorders.