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.