Improvement in some physicochemical and biological properties of LG106W by inclusion complexation with β-cyclodextrin and its derivatives

4-[3-Hydroxy-3-(2-hydroxy-5-methoxy-3,4,6-trimethyl-phenyl) propyl]-benzene-1,3-diol (LG106W) was synthesized as a novel skin-whitening agent. However, it has some formulation problems because of its low solubility in water and its instability. Inclusion complexation with cyclodextrins (CyDs) can be a tool for improving these problems. Inclusion complexes of LG106W with β-cyclodextrin (β-CyD) and its hydroxypropyl (HP-β-CyD) and dimethyl (DM-β-CyD) derivatives were evaluated by using a solubility method, a scanning electron microscope, a differential thermal analysis, and a powder X-ray diffractometer. We further investigated the cytotoxicity and in vitro skin permeation of the complexes. The relationship of inclusion complexation between LG106W and β-cyclodextrins was clearly reflected in the magnitude of the stability constant (DM-β-CyD > HP-β-CyD ≥ β-CyD). The stability of LG106W was improved by inclusion complexation with HP-β-CyD. The inclusion complexes had an activity similar to LG106W alone in the inhibition of melanin synthesis in B-16 melanoma cells, but showed lower cytotoxicity. The skin permeation of LG106W across excised hairless mouse skin was increased with the inclusion complexation, in the order of DM-β-CyD > HP-β-CyD > β-CyD. From the above results, it is suggested that the β-CyDs are reliable candidates for improving the availability of LG106W in cosmetic products.