Development of dihydrooxyresveratrol-loaded nanostructured lipid carriers for safe and effective treatment of hyperpigmentation.

Hyperpigmentation, a dermatological concern caused by increased melanin production, affects many people worldwide. Traditional skin-brightening products target inhibition of cellular tyrosinase activity but often contain harmful toxicants. Oxyresveratrol (OXR) is a robust tyrosinase inhibitor, but its instability, poor water solubility, and low skin permeation limit its use. This study aimed to overcome these challenges by modifying OXR to dihydrooxyresverstrol (DHO) and encapsulating both compounds into nanostructured lipid carriers (NLCs). The developed NLCs loaded with OXR (OXR-NLC) and DHO (DHO-NLC) achieve desirable physicochemical properties, high percentages of entrapment efficiency, and stability for at least three months during 4-40 ℃ of storage. DHO itself and NLC formulation of OXR dramatically enhanced the photostability of OXR. Additionally, NLC formulations significantly promoted controlled release and facilitated penetration through the skin-like hydrophobic membrane of OXR and DHO. Importantly, these NLC formulations exhibited no cytotoxicity on human keratinocyte cells up to 500 µg/mL and effectively reduced melanogenesis in B16F10 cells. Our findings indicate that DHO-loaded NLC offers a promising strategy for developing cosmeceutical products to address hyperpigmentation and promote skin lightening.