Green Arbutin-Chitosan Nanoparticles gel as an Eco-Friendly and Promising Product for Skin Lightening: In Vitro and In Vivo Assessment

Objective(s): In the present study, a cross-linking gelation method combined with ultrasound was employed to create arbutin (ARB)-incorporated chitosan (CHT) nanoparticles (NPs). This approach aims to enhance cutaneous absorption and improve anti-melanogenesis effects.Material and Methods: Environmentally-friendly preparation of NP, monitoring NP features, checking structure, animal safety application, cellular viability, and inhibitory assessment on melanin creation were performed.Results: The results showed that increasing the volume ratio of chitosan (CHT) to tripolyphosphate (TPP) from 10:1.25 to 10:5 resulted in a reduction of particle size from 1097.133 ± 28.655 nm to 215.666 ± 5.976 nm. Moreover, this CHT/TPP volume ratio increase from 10:1.25 to 10:5 enhanced the encapsulation efficiency, from 55.084 ± 4.283% to 97.151 ± 0.066%. Assessment of cutaneous absorption revealed that the ARB-CHT-NP gel delivered significantly more arbutin (ARB) to both the cutaneous layers (46.168 ± 3.313% or 810.094 ± 58.147 μg/cm²) and the receiver compartment (34.155 ± 2.699% or 599.314 ± 47.371 μg/cm²) compared to the ARB plain gel. In vitro cytotoxicity testing demonstrated that, in the presence of the optimal formulation, a higher percentage of cell survival was observed in the HFF cell line compared to kojic acid and ARB. Additionally, the ARB-CHT-NP gel exhibited greater cytotoxicity in the B16F10 cell line compared to the other groups. A cutaneous itching assay on Wistar rats showed no signs of sensitivity to the ARB-CHT-NP gel. Furthermore, ARB-CHT-NP inhibited melanogenesis more effectively than kojic acid and ARB. L-dopa auto-oxidation was also significantly inhibited by ARB-CHT-NP (56.971 ± 1.265%) compared to kojic acid (46.141 ± 1.169%) and ARB (41.308 ± 1.967%).Conclusion: Based on the results, the ARB-CHT-NP could serve as a prospective nanocarrier for ARB cutaneous application. Therefore, it is recommended that its use for treating melasma be considered.