Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.
Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.
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DOI：
10.3390/molecules26185722
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发表时间：
2021-09-21
期刊：
影响因子：
--
通讯作者：
Tang G
中科院分区：
文献类型：
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作者：
Lou Y;Yu K;Wu X;Wang Z;Cui Y;Bao H;Wang J;Hu X;Ji Y;Tang G
白藜芦醇(RSV)和虎杖苷(PD)已被广泛用于治疗几种慢性疾病，如动脉粥样硬化、肺纤维化和糖尿病等。然而，它们的低溶解度阻碍了它们的进一步应用。在这项工作中，我们证明了钯的溶解度可以通过与L-脯氨酸(L-Pro)的共结晶来提高。制备并表征了两种不同相的共晶，即RSV-L-Pro(RSV：L-Pro=1：2)和Pd-L-Pro(Pd：L-Pro=1：3)。与原液相比，Pd-L-Pro在水(pH 7.0)中的溶解度和溶出度增加了15.8%，而RSV-L-Pro的溶解度和溶出度降低了13.8%。四甲基偶氮唑盐(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法显示，两种化合物对肺癌细胞株A549和人胚肾细胞株HEK293均有明显的细胞毒作用，但对HEK293细胞的细胞毒作用明显减弱，其中Pd/Pd-L-Pro具有更好的生物安全性。本工作表明，易得、生物相容性好的L-Pro可作为佐剂优化呼吸道合胞病毒和帕金森病的理化性质，改善其药代动力学。
Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.