In vitro and in vivo evaluation of MHY908-loaded nanostructured lipid carriers for the topical treatment of hyperpigmentation

Abstract

Hyperpigmentation disorder, caused by the immoderate performance of tyrosinase, is a major abnormality of human skin. Downregulation of tyrosinase enzyme through tyrosinase inhibitors has emerged as an effective strategy for hyperpigmentation therapy. In this study, a newly synthesized tyrosinase inhibitor (MHY908) was loaded into a nanostructured lipid carrier (MHY908/NLC) for the topical treatment of hyperpigmentation. MHY908/NLCs were prepared by a reverse instilling technique of melt and ultrasonication. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and transmission electron microscopy (TEM) analyses showed that MHY908 was highly dispersed and encapsulated in NLC in an amorphous state. MHY908/NLCs exhibited a dual drug release kinetic (initial burst release followed by prolonged drug release), higher skin permeation, and significant occlusion effect (in vitro and ex vivo) than MHY908 solution. The anti-melanogenesis activity of MHY908/NLCs in a mouse model of UVB-induced hyperpigmentation was significantly higher than that of MHY908 solution. Furthermore, the in vitro cytotoxicity test revealed the non-toxicity of MHY908/NLCs to healthy fibroblast cells. Therefore, MHY908/NLC could serve as a promising topical delivery system for the treatment of hyperpigmentation.