Skin-whitening effect of hydroxypropyl-β-cyclodextrin/glabridin inclusion complex loaded on a dual thermo/pH-sensitive hydrogel

As a natural isoflavone compound, glabridin (GLD) has excellent skin-whitening properties, but its biomedical applications are greatly limited due to its poor water solubility and low skin permeability. In the current work, GLD was complexed with hydroxypropyl-(3-cyclodextrin (HP-(3-CD) to form a GLD/HP-(3-CD inclusion complex that would improve the water solubility and skin permeability by changing the physicochemical properties of GLD, including the formation of intermolecular hydrogen bonds and amorphous transformation. The cytotoxicity of GLD/HP-(3-CD on HaCaT keratinocytes is lower than that of GLD, while it has a more substantial inhibitory effect on melanin than GLD. Furthermore, a dual thermo- and pH-responsive hydrogel called PCG was established as the carrier of GLD/HP-(3-CD. The PCG hydrogel presented a porous structure, biodegradability, and excellent biocompatibility. GLD had a dual thermo- and pH-responsive release behavior from the PCG hydrogel and displayed an accelerated release rate at weakly acidic pH conditions compared to the neutral pH environment. Moreover, GLD/HP-(3-CD/PCG hydrogel can significantly inhibit melanin deposition in vivo. Taken together, this study provides a low toxicity and high efficiency new method for the application of GLD in biomedical fields, demonstrating its enormous potential in skin-whitening.