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Hyperpigmentation disorders are characterized by dark spots on the skin. Treatment for hypermelanosis involves the application of tyrosinase inhibitors, chemical peels, or lasers therapy, although they may cause skin irritation and other side effects. Potential natural alternatives for skin hyperpigmentation are quercetin (QT) and olive oil (OL) due to their antioxidant activity and anti-tyrosinase property. However, QT usage drawback is its low water solubility and high chemical instability that may be overcome with nanoencapsulation. To understand if QT and OL could be used as alternative to improve hypermelanosis, we evaluated the physical-chemical and biological properties of quercetin-loaded olive oil nanoemulsion (QT-NE). QT-NE was prepared by the high-energy emulsification method and, through the Box-Behnken design, we analyzed different concentrations of OL, surfactant mixture, and the agitation speed in relation to diameter and polydispersity index (PdI). The optimized formulation was characterized in terms of size, PdI, zeta potential, pH, electrical conductivity, stability and encapsulation efficiency. Besides, we evaluated  in vitro  antioxidant activity, tyrosinase inhibitory activity, and  in vitro  toxicity. The optimized QT-NE showed a size of 183.43 ± 9.53 nm with low PdI (∼0.19), zeta potential of −17.13 ± 0.61 mV, pH around 7, conductivity of 163.96 ± 8.92 µS/cm, and high encapsulation efficiency (∼99%). The QT-NE exhibited high antioxidant activity (∼92%) and inhibited 56% of tyrosinase activity, indicating its potential for free radical scavenging and reducing skin hyperpigmentation. Furthermore, no irritation was observed by HET-CAM. Thus, this nanoemulsion (NE) is a promising alternative for hypermelanosis and could substitute the current treatments.

Antioxidant and anti-tyrosinase activities of quercetin-loaded olive oil nanoemulsion as potential formulation for skin hyperpigmentation