Transdermal Delivery of Ruxolitinib Through CO 2 Ablative Laser ‐Assisted Silk Nanovehicle System for Improved Melanocyte Recovery in Vitiligo

ABSTRACT Vitiligo, an autoimmune skin disorder, is characterized by the loss of melanocytes, resulting in significant skin depigmentation. Ruxolitinib (RUX), which could target the JAK‐STAT signaling pathway, plays a crucial role in vitiligo treatment but faces great challenges in transdermal delivery. Here, we developed RUX‐laden silk fibroin nanoparticles to achieve transdermal delivery with the assistance of a CO 2 ablative laser. In vitro assays demonstrated that the RUX‐laden silk nanoparticles significantly inhibited the secretion of CXCL9 and CXCL10, and the phosphorylation of AKT2 and STAT3, indicating effective modulation of the JAK‐STAT pathway. The RUX‐laden silk nanoparticles exhibited excellent transdermal delivery capacity comparable to the Opzelura cream, which was further improved through a laser‐assisted strategy. In vivo studies revealed that the transdermally delivered RUX‐laden nanoparticles exhibited better skin toleration and significantly reduced the expression of multiple inflammatory cytokines such as CXCL9, CXCL10, IFN‐γ and TNF‐α, bringing substantial melanocyte recovery. The findings underscore the potential of silk‐based delivery systems in enhancing therapeutic efficacy against vitiligo, which would improve pigmentation restoration and inflammation modulation in skin disorders.