Isoliquiritigenin, a flavonoid extracted from licorice root, has been shown to be active against most cancer cells; however, its antitumor activity is limited by its poor water solubility. The aim of this study was to develop a stable isoliquiritigenin nanosuspension for enhanced solubility and to evaluate its in vitro cytostatic activity in A549 cells. The nanosuspension of isoliquiritigenin was prepared through wet media milling with HPC SSL (hydroxypropyl cellulose-SSL) and PVP K30 (polyinylpyrrolidone-K30) as stabilizers, and the samples were then characterized according to particle size, zeta-potential, SEM (scanning electron microscopy), TEM (transmission electron microscopy), DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction), FTIR (Fourier transform infrared spectroscopy), XPS (X-ray photoelectron spectroscopy), and in vitro release. The isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 had particle sizes of 238.1 ± 4.9 nm and 354.1 ± 9.1 nm, respectively. Both nanosuspensions showed a surface charge of approximately - 20 mV and a lamelliform or ellipse shape. The dissolution of isoliquiritigenin from the 2 nanosuspensions was markedly higher than that of free isoliquiritigenin. In vitro studies on A549 cells indicated that the cytotoxicity and cellular uptake significantly improved after treatment with both nanosuspensions in comparison to the isoliquiritigenin solution. Furthermore, cell apoptosis analysis showed a 7.5 - 10-fold increase in the apoptosis rate induced by both nanosuspensions compared with pure drug. However, the cytotoxicity of pure drug and nanosuspension on normal cells (HELF) was lower, which indicated both isoliquiritigenin nanosuspensions have low toxicity to normal cells. Therefore, the isoliquiritigenin nanosuspension prepared with HPC SSL and PVP K30 as stabilizers may be a promising approach to improve the solubility and cytostatic activity of isoliquiritigenin.

中文翻译：

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异甘草素纳米悬浮液增强 A549 肺癌细胞的细胞抑制作用

异甘草素是一种从甘草根中提取的黄酮类化合物，已被证明对大多数癌细胞具有活性；然而，其抗肿瘤活性受到其水溶性差的限制。本研究的目的是开发稳定的异甘草素纳米混悬液以提高溶解度，并评估其在 A549 细胞中的体外细胞抑制活性。以HPC SSL（羟丙基纤维素-SSL）和PVP K30（聚吡咯烷酮-K30）为稳定剂，通过湿介质研磨制备异甘草素纳米混悬液，然后根据粒径、zeta电位、SEM（扫描电子显微镜）对样品进行表征。 )、TEM（透射电子显微镜）、DSC（差示扫描量热法）、XRPD（X 射线粉末衍射）、FTIR（傅里叶变换红外光谱）、XPS（X 射线光电子能谱）、和体外释放。用 HPC SSL 和 PVP K30 制备的异甘草素纳米混悬液的粒径分别为 238.1 ± 4.9 nm 和 354.1 ± 9.1 nm。两种纳米悬浮液都显示出大约 - 20 mV 的表面电荷和层状或椭圆形。2 种纳米混悬液中异甘草素的溶出度明显高于游离异甘草素的溶出度。对 A549 细胞的体外研究表明，与异甘草素溶液相比，用两种纳米混悬液处理后细胞毒性和细胞摄取显着提高。此外，细胞凋亡分析显示，与纯药物相比，两种纳米混悬液诱导的细胞凋亡率增加了 7.5 - 10 倍。然而，纯药物和纳米混悬液对正常细胞（HELF）的细胞毒性较低，这表明这两种异甘草素纳米混悬液对正常细胞的毒性较低。因此，以HPC SSL和PVP K30为稳定剂制备的异甘草素纳米混悬液可能是提高异甘草素溶解度和细胞抑制活性的一种有前景的方法。