Anti-melanogenesis potential effect of green alginate nanoparticle of kojic acid as skin whitening product: in-vitro and in-vivo evaluation

Objective(s): This study evaluated a novel method combining ionic gelation and ultrasound for producing kojic acid (KJA)-loaded sodium alginate (AL) nanoparticles to enhance dermal delivery and anti-pigmentation effects.Material and methods: Green and eco-friendly preparation of nanoparticles, inspection of nanoparticle features, checking structure, animal safety administration, cellular vitality, and inhibitory evaluation of melanin synthesis were employed.Results: The results showed that increasing the volume ratio of AL/CaCl₂ from 10:2 to 10:10 reduced the mean particle size from 1691.767 ± 118.095 nm to 338.533 ± 8.429 nm. Moreover, the encapsulation efficiency was enhanced with this increase, rising from 8.051 ± 3.035% to 78.770 ± 3.155%. Skin permeability tests indicated that the KJA-AL nanoparticle gel delivered more KJA to the dermal layers (39.470 ± 3.606% or 519.432 ± 47.465 μg/cm²) and the receptor compartment (15.210 ± 0.468% or 200.170 ± 6.161 μg/cm²) compared to the plain KJA gel. The optimum formulation exhibited fewer toxic effects on HFF (Human Foreskin Fibroblast) cells, while a significant cytotoxic effect was observed on B16F10 cells with the KJA-AL nanoparticle. The non-irritating effect of the KJA-AL nanoparticle gel was confirmed through a dermal irritation test on Wistar rats. Two additional advantages of the present study include: i) greater inhibition of melanin formation with KJA-AL nanoparticles compared to free KJA, and ii) significant inhibition of L-dopa auto-oxidation by KJA-AL nanoparticles (82.224 ± 2.079%) compared to KJA solution (55.829 ± 2.881%).Conclusion: The results indicated that the KJA-AL nanoparticles produced in this study could serve as potential nano-vehicles for the dermal delivery of KJA. Additionally, they may offer an innovative solution for addressing hyper-melanogenesis-related issues.