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Objective(s): In this work, we loaded Auraptene (AUR) into nanostructured lipid carriers (NLCs) and performed an assessment on inhibitory activities of the obtained AUR-NLCs on melanogenesis. Materials and Methods: AUR-NLCs were prepared through a high shear homogenization and ultrasound method. Results: Entrapment efficiency and Particle size of the optimized formulation were 103.1±4.9 nm and 89.56±3.75. The TEM outcomes exhibited the spherical shape of our nanoparticles, while the DSC analysis revealed the lack of any drug-lipid incompatibility throughout the formulations. A prolonged drug-release was observed from AUR-NLCs when compared to the AUR-solution. According to results, this product can significantly attenuated the activity of cellular tyrosinase and ROS content with minimal cytotoxic effects in B16F10 cell line, which in contrast to AUR-solution. Moreover, the western blotting analysis was indicative of AUR-NLCs ability to inhibit melanogenesis through the suppression of MITF and act much more efficiently than AUR-solution.Conclusion: AUR-NLCs can offer merits as a natural anti-tyrosinase agent for the treatment of hyperpigmentory disorders.