Purpose: In the present research, a green technique (an ultrasonic method) was used to synthesize menadione sodium bisulfite (MSB) niosome (Menasome) which is used to improve dermal delivery and increase anti-melanogenesis activities. Methods: Various cholesterol: surfactant (Chol: Sur) ratios were investigated to optimize the Menasomes. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of MSB in nanoparticle form. Additionally, the optimized formulation was used to investigate ex-vivo skin absorption, in vivo skin irritation, in vitro cell survival, and anti-melanogenesis activity. Results: The results exhibited that increasing cholesterol (Chol) declined the average size of the Menasomes from 653.766±25.171 nm to 298.133±8.823 nm and increased entrapment efficiency 30.237±3.4204% to 83.616±2.550 %. The rat skin permeation study indicated that Menasome gel administered more MSB in dermal layers (439.000±36.190μg/cm2 or 23.827±1.964%) than MSB plain gel (286.200± 22.6μg/cm2 or 15.53±1.227%). In both the in vivo skin irritation test and the in vitro cytotoxicity experiment, the extended-release behavior of the enhanced Menasome demonstrated a minimal side effect profile. Furthermore, optimum Menasome inhibited melanin formation (37.426± 1.644% at 15μM) greater than free MSB (57.383±1.654%) considerably (p <0.05). Furthermore, Menasome 7 prevented L-dopa auto-oxidation in higher levels (95.140±2.439%) than pure MSB solution (83.953±1.629%). Conclusion: According to the study's findings, the prepared Menasome could be employed as a viable nanovehicle for MSB dermal delivery, a promising solution for the management of human hyperpigmentation disorders.
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