Response surface methodology - optimized niosomes encapsulating whole tomato extract: Release profile and mechanistic insights for UVB protection and anti-melanogenesis applications

• Box–Behnken RSM optimization produced niosomes (222 nm) with high entrapment efficiency (90 %). • FTIR and TEM confirmed successful encapsulation and uniform spherical morphology. • Dual-phase release: whole tomato extract followed the Higuchi model, while lycopene obeyed zero-order kinetics. • Optimized TNS niosomes protected HaCaT keratinocytes from UVB-induced damage. • TNS down-regulated MITF and tyrosinase in B16F10 cells, indicating strong anti-melanogenic potential for cosmetic use. This study presents the development and characterization of a novel niosome delivery system incorporating whole tomato extract for topical application. The formulation was optimized using a Box–Behnken design (BBD) by response surface methodology (RSM) to achieve high entrapment efficiency, small vesicle size, and low polydispersity index (PDI). The optimal formulation (2 mM Span 60, 1 mM cholesterol, 1 % extract) yielded an entrapment efficiency of 90.34 %, particle size of 222.06 nm, and PDI of 0.34. Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses confirmed successful encapsulation and nanoscale spherical morphology. In vitro release studies demonstrated distinct kinetic behaviors: the whole extract followed Higuchi model, while lycopene exhibited zero-order model. The optimized tomato extract–loaded niosomes (TNS) exhibited enhanced stability and demonstrated significant biological activity, including ultraviolet ̶ B (UVB) protection in immortalized human keratinocyte cell lines (HaCaT) and anti-melanogenic effects in murine melanoma cell lines (B16F10). Notably, tomato extract–loaded niosomes (TNS) significantly downregulated the expression of melanogenesis-related proteins, microphthalmia-associated transcription factor (MITF) and tyrosinase, as confirmed by Western blot analysis. These findings support the potential use of tomato extract-loaded niosomes (TNS) as multifunctional cosmetic ingredients for photoprotection and skin whitening applications.