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

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.