The Preparation of Glabridin-Loaded Liposomes and Their Inhibition Effects on Melanogenesis

Glabridin (GLA) is widely applied in cosmetics, pharmaceuticals, and food products; however, its application is limited by poor aqueous solubility, low stability, and low bioavailability. To overcome these disadvantages, Glabridin-Loaded Liposomes (L-GLAs) were prepared using a thin-film hydration-solvent evaporation method combined with high-pressure homogenization. The cumulative release rate of L-GLA within 96 h was higher than that of GLA. The stability of L-GLA was superior to that of GLA. The inhibitory effects and underlying mechanisms of GLA and L-GLA on B16 mouse melanoma cells were investigated. The IC₅₀ of L-GLA against B16 melanoma cells (84.66 μM) was lower than that of GLA (115.5 μM). Both compounds induced apoptosis in B16 cells, with L-GLA exhibiting greater potency. This effect may be related to the inhibition of B16 cell proliferation via G0/G1 phase arrest. Furthermore, in a melanin-producing B16 cell model, the melanin content and tyrosinase (TYR) activity in the GLA and L-GLA groups were lower than those in the model group, and L-GLA exerted a stronger inhibitory effect than GLA. Quantitative PCR analysis revealed that GLA and L-GLA reduced the mRNA expression levels of MITF, TYR, TRP-1, and TRP-2; and Western blotting further confirmed that the protein levels of these melanogenesis-related factors were consistently downregulated in B16 cells following photodynamic treatment. Mechanistically, these anti-melanogenic effects appeared to be associated with the downregulation of MITF and its downstream targets, potentially through the PKA/MITF and MAPK/MITF signaling cascades. Collectively, these findings suggest that liposomal encapsulation may enhance the anti-melanogenic and anti-proliferative bioactivity of GLA, which implies its potential as an improved formulation for biomedical and cosmetic applications.