Qibin Li,Yameng Wang,Qing Guo,Jie Cao,Yangjun Feng,Xue Ke
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8 + NKG2D + T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of 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.
危险品化学品经营许可证（带存储）