TPGS assists the percutaneous administration of curcumin and glycyrrhetinic acid coloaded functionalized ethosomes for the synergistic treatment of psoriasis

Combined therapy with anti-inflammatory drugs is preferred for the topical treatment of psoriasis, but the codelivery of drugs is restricted due to the lack of a suitable delivery system. Ethosomes with excellent transdermal properties are perfect as carriers for hyperplastic skin. Therefore, glycyrrhetinic acid-D-α-tocopherol acid polyethylene glycol succinate (GA-TPGS) was synthesized, which prevented the inflammation and lipid peroxidation damage, thus effectively stabilizing the psoriasis. Then GA-TPGS was surface-modified on the curcumin (Cur) loaded ethosomes to construct curcumin-loaded GA-TPGS-modified multifunctional ethosomes ([email protected]), exerting synergistic treatment for psoriasis. Using an interleukin-6-induced cell model, we found that [email protected] displayed desirable suppression of inflammation response and oxidative stress damage. Compared with the ethanol solution, the percutaneous penetration rates of Cur and GA in [email protected] were superior. In vivo microdialysis revealed similar results, suggesting an increase of transcutaneous absorption in [email protected] Fluorescence staining revealed that the cellular uptake and skin distribution were distinctly enhanced with the delivery by [email protected] After topical administration to imiquimod-induced psoriatic mice, the [email protected] group showed powerful treatment from inflammatory infiltration inhibition of Cur, glucocorticoid-like effects of GA and anti-lipid peroxidation of TPGS. Overall, GA-TPGS mediated ethosomes possess more advantageous transdermal properties and synergistic antipsoriatic efficacy.