Keratinocyte membrane-coated nanoparticle combined with epidermal-targeted microneedle for targeted therapy of atopic dermatitis.

Dysregulated keratinocyte apoptosis contributes to skin barrier impairment and Th2 immune imbalance in atopic dermatitis (AD). To address these issues, we developed MN-HCM@OA-NLC for targeted keratinocyte therapy, enhancing treatment precision and efficacy. The MN-OA-NLC has an insertion depth of approximately 70 μm, which can precisely deliver drugs into the viable epidermis, making the skin retention 2.51-fold that of OA-NLC. Due to the homologous targeting of HCM, the epidermal retention of MN-HCM@OA-NLC is 1.93-fold that of MN-OA-NLC. Totally, the skin retention of MN-HCM@OA-NLC is 16.9-fold higher than that of free OA, providing superior anti-atopic dermatitis efficacy. The MN-HCM@OA-NLC significantly downregulated the expression levels of IL-4, 5, and 13, rebalancing the Th1/Th2 immune response. Additionally, it reduced the epidermal thickness, mast cell count, and IgE expression by 50%, 34%, and 62%, respectively, leading to the alleviation of AD skin lesions. This study introduces a novel strategy that combines efficient delivery with precise targeting for AD treatment, and holds promise for extending therapeutic applications to other inflammatory skin conditions.