Transdermal Delivery of Ruxolitinib Through CO₂ Ablative Laser -Assisted Silk Nanovehicle System for Improved...

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 CO₂ 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.