Composite Dissolvable Microneedle-Enabled Local High-Dose Delivery of Endogenous Thiols for Efficient Allergic Dermatitis Treatment.

Allergic dermatitis (AD) requires long-term management, yet conventional systemic therapies are frequently limited by adverse effects and inadequate lesion-specific delivery. Herein, we report a mechanically reinforced composite dissolvable microneedle (MN) patch (L-Cys@HAMN) for localized endogenous thiol delivery in AD treatment. The patch consists of L-cysteine-loaded hyaluronic acid (HA) microneedle tips integrated with an elastic poly(n-butyl acrylate) (PBA) backing layer, enabling efficient force transmission and consistent skin penetration while minimizing structural deformation. Upon insertion, the dissolvable MN tips rapidly release L-cysteine into the viable epidermis, where it is enzymatically converted into hydrogen sulfide (H2S) to suppress inflammatory responses. In vitro studies demonstrated significant downregulation of proinflammatory cytokines, including TNF-α and IL-6. In a passive cutaneous anaphylaxis mouse model, L-Cys@HAMN markedly alleviated inflammatory infiltration and reduced local inflammatory burden compared with control treatments. In addition, the HA-based matrix provided auxiliary moisturizing and barrier-supporting effects. Collectively, this work presents a mechanically robust and therapeutically effective MN platform for localized endogenous thiol delivery and offers a promising strategy for AD management.