Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 14 3 2024 10 10 Menadione Sodium Bisulfite Loaded Rhamnolipid Based Solid Lipid Nanoparticle as Skin Lightener Formulation: A Green Production Beside In Vitro/In Vivo Safety Index Evaluation 623 633 10.34172/apb.2024.047 EN Fatemeh Asadpour Panbehchouleh https://orcid.org/0009-0000-4339-8432 Hossein Amani https://orcid.org/0000-0003-2732-3283 Majid Saeedi Journal Article 10.34172/apb.2024.047 2023 11 27 2024 06 19 Purpose: In the current investigation, an ultrasonic approach was performed to produce menadione sodium bisulfite-loaded solid lipid nanoparticles (MSB-SLNs) with rhamnolipid as bio-surfactant, which aimed to increase the dermal delivery and anti-pigmentation effect. Methods: To achieve optimum delivery for MSB, the impact of the ratio of two surfactants (rhamnolipid: Tween) on nanoparticle attributes and the respective functions were evaluated. In vitro diffusion process, in vitro cytotoxicity assay, determination of melanin content of melanoma cells, L-DOPA auto-oxidation inhibitory test, and skin irritation studies carried out to investigate the suitability of MSB formulation in dermal application. Results: The optimized nanoparticles showed an average particle size, zeta potential, polydispersity index (PDI), and drug entrapment efficiency of 117.26±1.12 nm, -6.28±0.33 mV, 0.262±0.002, 83.34±0.75% respectively in hydrophilic-lipophilic balance (HLB) of 12. The in vitro diffusion process demonstrated that MSB-SLN gel had a prolonged release pattern. The levels of MSB in the cutaneous layers (52.192±2.730% or 961.59±50.313 μg/cm2 ) and the receiver compartment (23.721±1.803 % or 437.049± 33.236 μg/cm2 ) for the MSB-SLN gel was higher than MSB simple and showed no cutaneous irritancy and toxicity in rats. MSB-SLN inhibited melanin formation and was remarkably higher than free MSB. MSB-SLN inhibited L-3,4- dihydroxyphenylalanine (L-DOPA) auto-oxidation to a greater extent (95.14±1.46%) than MSB solution (72.28±0.83%). Conclusion: This study’s observations revealed that the produced MSB-SLN might be used as a potential nano-vehicle for MSB dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.