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-β-cyclodextrin (HP-β-CD) to form a GLD/HP-β-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-β-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-β-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-β-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.

中文翻译：

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羟丙基-β-环糊精/光甘草胺包合物在热/pH 双敏感水凝胶上的皮肤美白效果


光甘草定 （GLD） 作为一种天然异黄酮化合物，具有优异的皮肤美白性能，但由于水溶性差，皮肤渗透性低，其生物医学应用受到很大限制。在目前的工作中，GLD 与羟丙基-β-环糊精 （HP-β-CD） 络合形成 GLD/HP-β-CD 包合物，该包合物将通过改变 GLD 的物理化学性质来提高水溶性和皮肤渗透性，包括分子间氢键的形成和非晶态转化。GLD/HP-β-CD 对 HaCaT 角质形成细胞的细胞毒性低于 GLD，同时对黑色素的抑制作用比 GLD 更显著。此外，一种称为 PCG 的热响应和 pH 响应双水凝胶被确立为 GLD/HP-β-CD 的载体。PCG 水凝胶具有多孔结构、生物降解性和优异的生物相容性。GLD 在 PCG 水凝胶中具有热响应性和 pH 响应性释放行为，与中性 pH 环境相比，在弱酸性 pH 条件下表现出加速的释放速率。此外，GLD/HP-β-CD/PCG 水凝胶可以显着抑制体内黑色素沉积。综上所述，本研究为 GLD 在生物医学领域的应用提供了一种低毒、高效的新方法，展示了其在皮肤美白方面的巨大潜力。