Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt.
Eur J Pharm Biopharm. 2021 Nov;168:166-183. doi: 10.1016/j.ejpb.2021.08.020. Epub 2021 Sep 2.
Hepatocellular carcinoma (HCC) is a prevalent liver cancer representing the fourth most lethal cancer worldwide. Trans-Resveratrol (T-R) possesses a promising anticancer activity against HCC. However, it suffers from poor bioavailability because of the low solubility, chemical instability, and hepatic metabolism. Herein, we developed T-R-loaded nanocochleates using a simple trapping method. Nanocarriers were optimized using a comprehensive in-vitro characterization toolset and evaluated for the anticancer activity against HepG2 cell line. T-R-loaded nanocochleates demonstrated monodispersed cylinders (163.27 ± 2.68 nm and 0.25 ± 0.011 PDI) and -46.6 mV ζ-potential. They exhibited a controlled biphasic pattern with minimal burst followed by sustained release for 72 h. Significant enhancements of Caco-2 transport and ex-vivo intestinal permeation over liposomes, with 1.8 and 2.1-folds respectively, were observed. Nanocochleates showed significant reduction of 24 h IC values compared to liposomes and free T-R. Moreover, an efficient knockdown of anti-apoptotic (Bcl-2) and cancer stemness (NANOG) genes was demonstrated. To the best of our knowledge, we are the first to develop T-R loaded nanocochleates and scrutinize its potential in suppressing NANOG expression, 2-folds lower, compared to free T-R. According to these auspicious outcomes, nanocochleates represent a promising nanoplatform to enhance T-R oral permeability and augment its anticancer efficacy in the treatment of HCC.
肝细胞癌 (HCC) 是一种常见的肝癌，是全球第四大致命癌症。反式白藜芦醇 (T-R) 具有抗 HCC 的潜在抗癌活性。然而，由于低溶解度、化学不稳定性和肝脏代谢，它的生物利用度较差。在此，我们使用简单的捕获方法开发了负载 T-R 的纳米 Cochleates。使用综合的体外特性工具集对纳米载体进行了优化，并评估了其对 HepG2 细胞系的抗癌活性。负载 T-R 的纳米 Cochleates 表现出单分散的圆柱体（163.27 ± 2.68nm 和 0.25 ± 0.011PDI）和-46.6mV ζ-电位。它们表现出控制的两相模式，初始突释较小，随后持续释放 72 小时。与脂质体相比，Caco-2 转运和离体肠渗透分别显著提高了 1.8 和 2.1 倍。纳米 Cochleates 与脂质体和游离 T-R 相比，显著降低了 24 小时 IC 值。此外，还证明了对凋亡抑制基因（Bcl-2）和癌症干性基因（NANOG）的有效下调。据我们所知，我们是第一个开发负载 T-R 的纳米 Cochleates 并研究其在抑制 NANOG 表达方面潜力的团队，与游离 T-R 相比，其表达水平降低了 2 倍。根据这些可喜的结果，纳米 Cochleates 代表了一种有前途的纳米平台，可以增强 T-R 的口服渗透性，并增强其在治疗 HCC 中的抗癌功效。
