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

Abstract 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 reactive oxygen species (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, Dex) in psoriasis. To conquer this problem, epigallocatechin‐3‐gallate (EGCG) is used to eliminate ROS production in psoriasis. Application of EGCG reduces ROS levels and improves the antipsoriasis effect of Dex in vitro. Benefiting from the unique characteristics of microneedle (MN) for transdermal drug delivery, a dissolvable MN patch containing EGCG and Dex (DEX/EGCG‐MN) is constructed, which can directly codelivery the two elements to the lesion area without stratum corneum barrier. The MN alleviates psoriasis‐like manifestations in imiquimod‐induced psoriasis mouse model, indicated by epidermal thickness and dorsal skin signs. Besides, DEX/EGCG‐MN corrects 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, the MN also ameliorates the hyperproliferation of keratinocytes in psoriatic lesions. It is believed that this approach may offer insights for further developing antipsoriasis assays.