Dual-continuous microneedle patch integrating transdermal delivery of pH-sensitive licorzinc MOFs and Zn2+ hydrogel sensors for treating alopecia areata

Licorzinc is a commonly used immunomodulator, but faces poor water solubility, high oral dose, and side effects of zinc accumulation by long-term administration. Herein, a new licorzincform was developed by adsorbing glycyrrhizic acid (GA) into zeolitic imidazolate framework-8 (GA@ZIF-8) with superior solubility and acid-responsive drug release properties. Then, a dual-continuous microneedle patch was developed for simultaneous transdermal delivery of GA@ZIF-8 and monitoring Zn 2+ in local tissues, where dissolving microneedles as a drug delivery unit were fabricated from hyaluronic acid. In contrast, swollen hydrogel microneedles as a diagnostic unit were prepared from double cross-linking of N-acryloyl-glycinamide and α-methylacrylic acid and hybridized with Eu 3+ and terpyridine (TPy). The microneedles for transdermal GA@ZIF-8 delivery were completely dissolved in 2 min, which improved the cyclophosphamide-induced hair follicle recession in mice by reducing CD8 + NKG2D + T cells infiltration, inhibiting Jak receptor activation, and decreasing IL-15 and IFN-γ. Additionally, as a sensor unit, the microneedles rapidly absorbed water swelled when stabbed into the skin, and fluoresced red when exposed to 365 nm light. Zn 2+ in the inter tissue fluid competes with Eu 3+ in the TPy-Eu 3+ complex and coordinates with Tpy, which triggers a change in fluorescence. Notably, the detection Zn 2+ concentration range was 10 –8 M–10 –1 M, and it was not disturbed by metal ions including Na + , K + , Mg 2+ , and Ca 2+ , suggesting that it is competent to be applied as a real-time chemosensor of Zn 2+ . Collectively, this newly designed system with both therapeutic and diagnostic functions provides a new strategy for treating zinc-related diseases.