A Novel Transdermal Plasmid-Dimethylsulfoxide Delivery Technique for Treatment of Psoriasis

Abstract

Background: Psoriasis is a chronic and relapsing inflammatory skin disease associated with various immunologic abnormalities. Repeated subcutaneous injection of interleukin-4 (IL-4) has been established as an effective treatment to counteract psoriasis. Objective: We investigated whether gene therapy using IL-4 expression plasmid (pIL-4) via transdermal delivery was an alternative treatment for psoriasis. In our experiment, dimethylsulfoxide (DMSO) was used as a penetration enhancer. Methods: At first, the penetration efficiency of the complex of reporter plasmid accompanied by DMSO was investigated both in vitro and in vivo. Then, the antipsoriasis efficiency of the treatment with pIL-4-DMSO was tested in mice. Results: The expression of the reporter gene was detected in epidermis and dermis both in vitro and in vivo. More importantly, the psoriasis symptoms were relieved, and significant reductions in some psoriasis-associated factors were observed after pIL-4-DMSO treatment. Conclusion: We conclude that the topical application of pIL-4-DMSO can treat psoriasis to a significant extent.

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

“…DMSO has been shown to promote the permeation of, for example, antiviral agents, steroids and antibiotics 9 . We also confirmed that 10% DMSO was the optimal transdermal delivery formula for further examination in vivo 8 , 10 . These results provide a foundation for increasing the efficiency of gene transdermal penetration with DMSO.…”

Interleukin 4 or Cytokine Antagonists? Time to Change the Search for Novel Psoriasis Therapies

“…In this issue Zhang et al [16] show that topical application of a plasmid encoding the IL-4 gene allows transdermal delivery of IL-4 and strongly improves skin inflammation in a model disease that closely mimicks psoriasis [17] . In this model, mice express the gene for the vascular endothelial growth factor in the basal keratinocytes.…”

“…While under normal conditions, activation of Th cells results in Th1 or Th17 cells, priming of Th cells in the presence of either endogenous or exogenous IL-4 leads to a Th2 phenotype that is characterized by the production of IL-4 and strongly suppresses inflammation such as psoriasis in humans [14,22] , probably also multiple sclerosis and all experimental inflammatory diseases studied so far under in vivo conditions [15,16,18,19] . This is also the case in humans, as shown first in vitro and then in vivo [14,22] .…”

IL-23 Induces Atopic Dermatitis-Like Inflammation Instead of Psoriasis-Like Inflammation in CCR2-Deficient Mice

“…Recent studies have demonstrated that skewing CD4 + T cell phenotype within psoriatic plaques to a Th2-type immune response can ameliorate disease [31], [32], [33]. Treatment of psoriasis patients with subcutaneous injections of IL-4 polarizes lesional T cell responses to a Th2-type and decreases psoriasis severity [31].…”

“…Treatment of psoriasis patients with subcutaneous injections of IL-4 polarizes lesional T cell responses to a Th2-type and decreases psoriasis severity [31]. Similarly, transdermal delivery of IL-4 expression plasmid ameliorates disease in a mouse model of psoriasis [32], [33]. Thus, induction of a Th2 phenotype of skin infiltrating lymphocytes correlates with disease improvement.…”