Triple-Loaded Nanoemulsions Incorporating Coffee Extract for the Photoprotection of Curcumin and Capsaicin: Experimental and Computational Evaluation.

: This study aims to present a strategic approach to enhancing the photostability and antioxidative resilience of curcumin and capsaicin by integrating selected natural stabilizers within a nanoemulsion-based delivery system. : Coffee extract ( Linn.), along with its active components and vitamin E-containing natural oils, was assessed in terms of improving the photostabilizing and antioxidative retention abilities of curcumin and capsaicin. An optimized ratio of the active mixture was then loaded into a nanoformulation. : The analysis of active contents with validated high-performance liquid chromatography (HPLC), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays confirmed the stabilization enhancement after irradiation with UV and white light for 72,000-84,000 lux hours. The optimized combination of coffee extract with turmeric and chili mixtures loaded into the optimized nanoemulsion enhanced the half-lives (T) of curcumin and capsaicin by 416% and 390%, respectively. The interactions of curcumin and capsaicin with caffeine and chlorogenic acid were elucidated using computational calculations. Interaction energies (E), HOMO-LUMO energy gap (HLG) analysis, and global reactivity descriptors revealed hydrogen bonding interactions be-tween capsaicin and chlorogenic acid, as well as between curcumin and caffeine. : By leveraging the synergistic antioxidative properties of coffee extract and vitamin E within a nanoemulsion matrix, this study overcomes the intrinsic stability limitations of curcumin and capsaicin, offering a robust platform for future pharmaceutical and nutraceutical applications.