Development and Evaluation of Retinol-Curcumin Nanoemulsions for Potential Topical Delivery

Retinol and curcumin are bioactive compounds with promising dermatological applications; however, their poor aqueous solubility, instability, and limited bioavailability may restrict their therapeutic performance. This study aimed to develop and evaluate retinol-curcumin nanoemulsions (RCNEs) as a co-delivery system with antioxidant, anti-inflammatory, antibacterial, and in vitro safety potential. Curcumin and retinol were quantified using UV-visible spectrophotometry, and the nanoemulsions were prepared by mixing the aqueous and oily phases followed by sonication. The prepared formulations were evaluated for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, loading efficiency, and stability under different storage conditions. Antioxidant activity was determined using the DPPH radical scavenging assay, cytotoxicity was evaluated using the MTT assay on EaHY.926 endothelial cells, anti-inflammatory activity was assessed by measuring TNF-α inhibition, and antibacterial activity was tested against Staphylococcus aureus and Escherichia coli using the Kirby-Bauer well diffusion method. The optimized RCNE formulation showed an average particle size of 117 ± 0.1 nm, PDI of 0.138 ± 0.010, and zeta potential of −12.7 ± 0.2 mV. Encapsulation efficiencies were 77.0±1.1% for curcumin and 91.1±0.8% for retinol. RCNEs exhibited the strongest antioxidant activity, with an EC50 of 56.04±1.95 µg/mL compared with 90.03±3.15 µg/mL for curcumin nanoemulsions and 227.3±8.4 µg/mL for retinol nanoemulsions (p≤0.05). The RCNE formulation also produced the highest TNF-α inhibitory activity, reducing TNF-α concentration to 76.5±5.2 pg/mL and achieving 86.2±1.8% inhibition, which was significantly higher than curcumin nanoemulsions (36.6±2.4%) and retinol nanoemulsions (39.1±2.1%) (p≤0.05). No marked cytotoxicity was observed within the tested concentration range. The formulation also demonstrated antibacterial activity against both tested bacterial strains, with larger inhibition zones against E. coli. These findings suggest that RCNEs may serve as a promising in vitro platform for co-delivering retinol and curcumin in topical pharmaceutical applications.