Development of an Effective Psoriasis Treatment by Combining Tacrolimus-Encapsulated Liposomes and Iontophoresis.

Psoriasis is a chronic T-cell-mediated autoimmune skin disease. Tacrolimus (FK506) is commonly used treatment for psoriasis. However, since the molecular weight of FK506 is more than 500 Da, its skin penetration is limited, so that there is a need to improve the penetrability of FK506 to allow for more effective treatment. To this end, we employed iontophoresis (ItP), which is a physical, intradermal drug delivery technology that relies on the use of weak electric current. Previous findings suggest that activation of cell signaling by the weak electric current applied during ItP may affect the expression of inflammatory cytokines, leading to aggravation of psoriasis. In this study, we analyzed the effect of ItP on the expression of various inflammatory cytokines in the skin, and subsequently examined the therapeutic effect of ItP using negatively-charged liposomes encapsulating FK506 (FK-Lipo) in a rat psoriasis model induced by imiquimod. We found that ItP (0.34 mA/cm, 1 h) did not affect mRNA levels of inflammatory cytokines or epidermis thickness, indicating that ItP is a safe technology for psoriasis treatment. ItP of FK-Lipo suppressed the expression of inflammatory cytokines induced by imiquimod treatment to a greater extent than skin treated with FK506 ointment for 1 h. Furthermore, epidermis thickening was significantly suppressed only by ItP of FK-Lipo. Taken together, results of this study demonstrate the successful development of an efficient treatment for psoriasis by combining FK-Lipo and ItP, without disease aggravation associated with the weak electric current.