Microneedles Loaded with Dexamethasone and Epigallocatechin-3-gallate Reverse the Imbalance of Subcutaneous Immune Homeostasis for the Treatment of Psoriasis

Maintaining the homeostasis of the skin's immune microenvironment is crucial for skin's health. In inflammatory skin conditions (like psoriasis), the immune microenvironment is dysregulated, including ROS accumulation and T cell overactivation. In addition to promoting inflammation and excessive keratinocyte proliferation, ROS upregulation in psoriasis also induces glucocorticoid resistance, which poses a significant challenge to the effectiveness of glucocorticoid treatment (e.g., dexamethasone) in psoriasis. To conquer this problem, we used epigallocatechin-3-gallate (EGCG) to eliminate ROS production in psoriasis. Application of EGCG reduced ROS levels and improved the anti-psoriasis effect of Dexamethasone (Dex) in vitro. Benefiting from the unique characteristics of microneedle for transdermal drug delivery, we construct a dissolvable microneedle (MN) patch containing EGCG and Dex (DEX/EGCG-MN), which can directly codelivery the two elements to the lesion area without stratum corneum barrier. Our MN alleviates psoriasis-like manifestations in imiquimod (IMQ)-induced psoriasis mouse model, indicated by epidermal thickness and dorsal skin signs. Besides, DEX/EGCG-MN corrected the disorder of immune cells, including innate and acquired immune cells. As a result, it mediates the balance in the skin's immune microenvironment. Meanwhile, our MN also ameliorated the hyperproliferation of keratinocytes in psoriatic lesions. We believe this approach may offer insights for further developing anti-psoriasis assays. This article is protected by copyright. All rights reserved