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 ۱۰:۱.۲۵ to ۱۰:۵ resulted in a reduction of particle size from ۱۰۹۷.۱۳۳ ± ۲۸.۶۵۵ nm to ۲۱۵.۶۶۶ ± ۵.۹۷۶ nm. Moreover, this CHT/TPP volume ratio increase from ۱۰:۱.۲۵ to ۱۰:۵ enhanced the encapsulation efficiency, from ۵۵.۰۸۴ ± ۴.۲۸۳% to ۹۷.۱۵۱ ± ۰.۰۶۶%. Assessment of cutaneous absorption revealed that the ARB-CHT-NP gel delivered significantly more arbutin (ARB) to both the cutaneous layers (۴۶.۱۶۸ ± ۳.۳۱۳% or ۸۱۰.۰۹۴ ± ۵۸.۱۴۷ μg/cm²) and the receiver compartment (۳۴.۱۵۵ ± ۲.۶۹۹% or ۵۹۹.۳۱۴ ± ۴۷.۳۷۱ 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 B۱۶F۱۰ 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 (۵۶.۹۷۱ ± ۱.۲۶۵%) compared to kojic acid (۴۶.۱۴۱ ± ۱.۱۶۹%) and ARB (۴۱.۳۰۸ ± ۱.۹۶۷%).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.

کلیدواژه ها:

Arbutin ، Chitosan ، Nanoparticle ، anti-melanogenesis ، Environmentally preparation