Enhanced Skin Delivery of Mussel Adhesive Protein Modified Pluronic F127 Micelles Loaded with Curcumin for Effective Topical Treatment of Psoriasis

Background: Psoriasis is a long-term inflammatory skin disorder that significantly impacts the physical and psychological well-being of those affected. Curcumin (Cur) is a natural compound that holds promise for the topical management of psoriasis. However, the barrier property of the stratum corneum (SC) and the insufficient retention ability of the drug in the skin have severely restricted the clinical efficacy of Cur. To overcome these limitations, we introduced mussel adhesive protein (MAP) for its superior bioadhesive properties, and developed Cur-loaded MAP modified Pluronic F127 micelles (MAP-F127/Cur) to improve the skin permeation and retention of Cur and enhance the therapeutic effect on psoriasis. Methods: In this study, MAP-F127 was synthesized via chemical synthesis. MAP-F127/Cur was prepared using the thin-film hydration method, and the physicochemical properties of the formulation were characterized. In addition, porcine skin was employed as an in vitro model to evaluate the skin permeation of the formulation and to elucidate the interaction mechanism between the formulation and the skin. Furthermore, the therapeutic efficacy of the formulation against psoriasis was assessed using an imiquimod-induced psoriasis mouse model. Results: The prepared MAP-F127/Cur had a regular spherical shape and good dispersion, and could efficiently load Cur in the amorphous form. The skin retention of MAP-F127/Cur was notably elevated in comparison to both the Cur-loaded Pluronic F127 micelles (F127/Cur) and Cur solution ( p < 0.01). Studies on the skin permeation mechanism showed that MAP-F127/Cur could break through the restriction of the skin barrier by regulating lipid arrangement and keratin conformation in the SC, forming a long-acting drug reservoir in the epidermal layer. Furthermore, in the imiquimod-induced psoriasis mouse model, MAP-F127/Cur demonstrated a significantly enhanced therapeutic effect. Conclusion: : This study not only provides a new delivery strategy for Cur in the treatment of psoriasis, but also offers an important reference for designing transdermal delivery systems for other dermatological drugs. Keywords: curcumin, mussel adhesive protein, pluronic F127 micelles, topical delivery, psoriasis