Ruxolitinib-loaded Hyalurosomes: A novel nanoplatform for enhanced topical management of vitiligo

Vitiligo is a chronic autoimmune skin disorder characterized by melanocyte destruction and progressive depigmentation, posing significant challenges. Ruxolitinib (RUX), a Janus kinase inhibitor, has demonstrated efficacy in modulating immune-mediated melanocyte damage. However, its topical application is limited by poor skin penetration and the need for prolonged treatment. This study aimed to develop and evaluate a ruxolitinib-loaded hyalurosomal (RUX-HS) nano-delivery system to enhance to enhance skin permeation, skin retention, and therapeutic performance. RUX-HS formulations were prepared and characterized, exhibiting nanosized vesicles (174 nm), narrow size distribution, high entrapment efficiency (86%), and suitable zeta potential (−24.5 mV), indicating good stability. Transmission electron microscopy (TEM) confirmed spherical core–shell vesicles, while attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated distinctive functional groups. In vitro release studies demonstrated sustained drug release (45% over 24 h) compared to conventional formulations. Ex vivo permeation studies using human skin showed significantly enhanced drug permeation (2.98-fold) and retention (3.85-fold). In vivo evaluation using a hydroquinone-induced vitiligo mouse model demonstrated superior therapeutic efficacy, with near-complete repigmentation and restoration of hair color. Biochemical analysis revealed increased tyrosinase activity (1.96-fold), elevated glutathione (GSH), and reduced malondialdehyde (MDA) and nitric oxide metabolites (NOx), indicating improved oxidative balance. Additionally, tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were significantly reduced (2.5-fold), while protease-activated receptor-2 (PAR-2) expression was restored (2-fold). Histopathological and immunohistochemical (Melan-A) analyses confirmed enhanced melanocyte regeneration and restoration of normal skin architecture. Notably, RUX-HS achieved superior efficacy at a 7.5-fold lower dose than marketed RUX cream, with no observed toxicity. These findings highlight RUX-HS as a promising, safe, and effective nanoplatform for targeted vitiligo therapy.