Baricitinib-loaded EVs promote alopecia areata mouse hair regrowth by reducing JAK-STAT-mediated inflammation and promoting hair follicle regeneration.

Abstract

Alopecia areata (AA) is a common and recurrent type of hair loss. Despite oral administration of baricitinib exerts a good effect on refractory AA, the long-term administration of baricitinib carries significant side effects, poor compliance, and the efficacy is difficult to maintain after drug withdrawal. Therefore, the exploration of a safe and effective local administration of baricitinib to treat AA is of great clinical importance. However, baricitinib has a large molecular weight and is barely soluble in water, while the hair follicle lies deep, thus conventional topical dosage forms are ineffective. This study investigated the efficacy of local injection of baricitinib-loaded mesenchymal stem cell exosomes (EVs) in the treatment of AA. First, we constructed baricitinib loaded EVs (EV-B) and established AA mouse model by intravenously injection with murine INF-γ according to previous literature reports. The therapeutic effects of EV-B on hair regrowth were recorded and the underlying mechanism was also analyzed by Luminex protein biochip test and western-blot. Compared to control group, the baricitinib, EV and EV-B groups exhibited improved hair coverage in the AA mouse model. Besides, EV-B group achieved the optimal effect. The underlying mechanism might be attributed to the improvement of drug delivery efficiency as well as the synergistic effect of EVs, leading to better inhibition of JAK-STAT pathway and upregulation of the Wnt/β-catenin pathway. Our findings proved the effectiveness of EV-B on the treatment of AA, and might provide a new therapeutic approach for AA in future clinical application.