The skin delivery of tofacitinib citrate using transethosomes and hybridized ethosomes/nanostructured lipid carriers for vitiligo therapy: Dermatopharmacokinetics and in vivo assays

Vitiligo is an autoimmune disease where its current treatment strategies are lengthy in course and do not guarantee complete cure. Tofacitinib citrate (JAK inhibitor) is a potential cure of vitiligo through halting JAK-STAT pathway preventing the destruction of melanocytes. The dermato-pharmacokinetics of the prepared transethosomes (Et) and the hybridized ethosomes/nanostructured lipid carriers (Eth/NLC), namely formulations; M.E-Cr and M.E-S.M, were evaluated. In addition, in vivo studies on C57/BL6 vitiligo mouse model were conducted to confirm effectiveness of Tofacitinib citrate delivery. The results unveiled that the transethosomes (359.46 ± 11.82 nm) were suitable for dermal delivery while M.E-Cr (179.64 ± 11.16 nm), a hybrid Eth/NLC formulation, was mostly suitable for transdermal delivery. Nevertheless, another hybrid formulation, M.E-S.M (253.60 ± 14.64 nm), was apt for both dermal and transdermal delivery. The histopathology confirmed re-pigmentation of mice skin where formulations Et and M.E-S.M showed severe pigmentation compared to the control healthy and induced mice. On the other hand, M.E-Cr showed mild pigmentation. Immunohistochemical assay was performed to evaluate infiltration of CD 8+T-lymphocytes where mild infiltration was observed. However, the systemic IFN-γ was significantly reduced in case of M.E-Cr and M.E-S.M. The present work proposed potential effective formulations to improve the treatment of vitiligo with potential reduction in the total therapeutic dose, drug's side effects, and treatment costs.