Enhanced oral permeability of Trans-Resveratrol using nanocochleates for boosting anticancer efficacy; in-vitro and ex-vivo appraisal

El-Melegy, Mohamed G.; Eltaher, Hoda M.; Gaballah, Ahmed; El-Kamel, Amal H.

Abstract

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 IC50 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.

Citation

El-Melegy, M. G., Eltaher, H. M., Gaballah, A., & El-Kamel, A. H. (2021). Enhanced oral permeability of Trans-Resveratrol using nanocochleates for boosting anticancer efficacy; in-vitro and ex-vivo appraisal. European Journal of Pharmaceutics and Biopharmaceutics, 168, 166-183. https://doi.org/10.1016/j.ejpb.2021.08.020

• Journal Article Type: Article
• Acceptance Date: Aug 27, 2021
• Online Publication Date: Sep 9, 2021
• Publication Date: 2021-11
• Deposit Date: Apr 26, 2023
• Publicly Available Date: Jun 16, 2023
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Electronic ISSN: 1873-3441
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 168
• Pages: 166-183
• DOI: https://doi.org/10.1016/j.ejpb.2021.08.020
• Public URL: https://nottingham-repository.worktribe.com/output/8771415
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0939641121002320?via%3Dihub