A transdermal drug delivery system based on estradiol liposomes enhances the alleviation of psoriatic skin inflammation

Psoriasis is a highly prevalent and chronic inflammatory skin disease, the initiation and progression of psoriasis is closely associated with immune activation and abnormal proliferation of keratinocytes. Estradiol (E2) plays a significant role in psoriasis pathogenesis, exhibits favorable anti-inflammatory effects and could suppress the inflammation characteristic of psoriasis. However, the transdermal efficiency of current E2 formulations is generally low, and alternative administration routes may be associated with adverse effects. Here, we present a transdermal delivery system of liposome gel designed to facilitate the transdermal delivery of E2 to ameliorate psoriatic skin inflammation. The phospholipids within the liposomes interact with the lipids of the stratum corneum, permeating dense skin structure and thereby increasing the intradermal retention of the drug. The gel matrix provides structural support, which reduces fluidity of the system, enhances liposome stability, and effectively prevents the rapid clearance of the drug from skin surface. Extensive in vitro and in vivo studies were conducted to evaluate the therapeutic efficacy of E2 liposome gel in treating psoriasis. The results showed that E2 liposome gel could effectively penetrate the skin barrier and deliver E2 to the site of inflammation. This led to a significant inhibition of the production of interleukin-1β (IL-1β), interleukin-23 (IL-23), and interleukin-17A (IL-17A), effectively suppressed the abnormal proliferation of keratinocytes, thereby ameliorating psoriatic skin inflammation. In conclusion, this study provides a safer and more efficient strategy for the sustained and controlled release of E2. This not only offers a more promising therapeutic approach for psoriasis, but also provides new insights for exploring the role of E2 in other inflammatory diseases.