Supramolecular cyclodextrin deep eutectic solvent-strengthened chitosan eutectogel as a novel percutaneous delivery system of resveratrol for anti-psoriasis.

Psoriasis is a chronic and incurable inflammatory skin disease usually requiring long-term disease management. Natural phytochemical resveratrol (RES) has been known for high efficiency and low toxicity, exhibiting good anti-psoriasis potential. However, its biological activity is limited by poor solubility, chemical instability, and insufficient skin retention. Herein, we developed an adhesive eutectogel loaded with RES constructed through electrostatic and hydrogen bonding cross-linking between cyclodextrin-levulinic acid supramolecular deep eutectic solvent (DES) and chitosan (CS). A series of characterizations combined with molecular dynamics simulations demonstrated that such DES not only significantly increased the solubility and stability of RES, but also acted as the cross-linker and plasticizer in eutectogel preparation. When applied to the skin surface, the eutectogel formed a soft film in situ that established tight contact with the skin, thereby enhancing RES sustained penetration into the skin. In an imiquimod-induced psoriasis-like mice model, the eutectogel effectively alleviated psoriasis symptoms, inhibited the excessive proliferation of keratinocytes, and regulated the expression of IL-23/IL-17 axis-related factors, whose therapeutic effect was better than that of commercially available calcipotriol ointment. Overall, The DES-strengthened eutectogel offers a promising topical drug delivery platform for psoriasis treatment and expands the applications of green polysaccharide medical materials.