Topical delivery of tofacitinib citrate loaded novel nanoemulgel for the management of 2,4-Dichlorodinitrobenzene induced atopic dermatitis in mice model
Abstract
Tofacitinib is an inhibitor of Janus kinases (JAK), which is approved to manage moderate to severe conditions of rheumatoid arthritis, showing inadequate response or intolerance to methotrexate. Currently, several clinical trials are in progress, emphasizing the potential study of tofacitinib in managing inflammatory skin disorders like atopic dermatitis and psoriasis. The present research study includes the formulation and characterization of tofacitinib citrate-loaded nanoemulgel for the topical treatment of atopic dermatitis. Tofacitinib exhibited enhanced solubility in the combination of eugenol (oil) and dimethyl sulfoxide (co-solvent), tween-20 (surfactant), along with Transcutol-P (co-surfactant). The study concentration selected for the present work is 0.5% (w/w) of tofacitinib citrate loaded into nanoemulgel. The tofacitinib citrate-loaded nanoemulsion was prepared by the spontaneous nanoemulsion method and characterized by particle size, PDI, transmittance and visual appearance.
Further, a novel nanoemulgel was prepared using SEPINEO? P 600 gel base and evaluated for its pH, viscosity, spreadability, release behavior and drug content for two months. The present work also evaluated the efficacy of optimized tofacitinib citrate-loaded nanoemulgel in the 2,4-Dinitrochlorobenzene induced atopic dermatitis-like symptoms in the BALB/c mice model. In vivo efficacy study demonstrated a significant reduction in dermatitis score and pro-inflammatory cytokine levels in skin homogenates of tofacitinib citrate nanoemulgel treated mice group. Results from animal studies depicted an enhanced activity of tofacitinib citrate nanoemulgel compared to free drug. The tofacitinib citrate nanoemulgel could be a clinically translatable, safer topical formulation for managing atopic dermatitis.