Institute of Chemical Kinetics and Combustion, Institutskaya St. 3, 630090 Novosibirsk, Russia.
Institute of Solid State Chemistry and Mechanochemistry, Kutateladze St. 18, 630128 Novosibirsk, Russia.
Molecules. 2021 Feb 26;26(5):1270. doi: 10.3390/molecules26051270.
Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stability and solubility at pH > 6 when the GA molecule is fully deprotonated. It means the higher release rate of the drug in a neutral and basic environment compared with acid media. These results could form the basis of follow-up studies of GA self-associates as pH-controlled drug delivery systems.
甘草酸，又称甘草甜素（GA），是甘草根中的主要活性成分，自古以来就在中医和日本医学中广泛应用。然而，直到最近几十年，人们才发现 GA 具有一种新颖而不寻常的性质，它可以与多种亲脂性药物形成水溶性的超分子配合物。与其他已知的给药系统相比，这些配合物具有显著的优势，特别是由于 GA 自组装体的强 pH 敏感性。在本研究中，研究了降压和抗心律失常药物硝苯地平与 GA 在不同 pH 值下的超分子配合物形成，这些 pH 值对应于 GA 不同程度的解离，包括 GA 的完全解离状态。NMR 实验和分子动力学模拟都证明了在 GA 的所有解离状态下都存在与 GA 的硝苯地平配合物。然而，光吸收实验表明，当 GA 分子完全去质子化时，在 pH 值>6 时配合物的稳定性和溶解度会降低。这意味着与酸性介质相比，在中性和碱性环境中药物的释放速度更高。这些结果可以为后续研究 GA 自组装体作为 pH 控制的药物传递系统奠定基础。
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