Capsaicin and diclofenac coloaded nanoemulsion gel optimized by quality by design approach of for the treatment of rheumatoid arthritis.

AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with progressive joint damage and pain. The present study aimed to develop and optimize a capsaicin - diclofenac-loaded nanoemulgel incorporating clove and olive oil for enhanced topical delivery and therapeutic efficacy in RA management. MATERIALS AND METHODS: Central composite design was employed to optimize nanoemulsion composition using oil (5-10%) and Smix (15-20%) as independent variables. The optimized formulation was characterized for particle size, polydispersity index (PDI), zeta potential, transmittance, morphology, rheology, antioxidant activity, cytotoxicity, cell viability, and skin permeation behavior. RESULTS: Optimized formulation exhibited particle size below 200 nm, PDI below 0.3, zeta potential below -10 mV, and transmittance of 92.6%, indicating good stability. Microscopic studies confirmed spherical globules. The nanoemulgel showed skin-compatible pH and non-Newtonian rheological behavior. Enhanced in vitro permeation, deeper skin penetration, and superior antioxidant activity (76.80 ± 2.90%) were observed compared to the conventional suspension. The formulation also demonstrated higher cytotoxicity against inflammatory U937 macrophage-like cells (58.2% at 50 μg/mL), lower IC50 (28.8 μg/mL), and improved MG-63 cell viability (85.8%). CONCLUSIONS: The developed nanoemulgel demonstrated improved physicochemical characteristics, enhanced skin permeation, and promising anti-inflammatory potential, suggesting its suitability as an effective topical delivery system for rheumatoid arthritis management.