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      Assessment of a New Ginsenoside Rh2 Nanoniosomal Formulation for Enhanced Antitumor Efficacy on Prostate Cancer: An in vitro Study

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          Abstract

          Introduction

          Ginsenoside Rh2, purified from the Panax ginseng root, has been demonstrated to possess anticancer properties against various cancerous cells including colorectal, breast, skin, ovarian, prostate, and liver cancerous cells. However, the poor bioavailability, low stability on gastrointestinal systems, and fast plasma elimination limit further clinical applications of Ginsenoside Rh2 for cancer treatments. In this study, a novel formulation of niosomal Ginsenoside Rh2 was prepared using the thin film hydration technique.

          Methods

          The niosomal formulation contained Span 60 and cholesterol, and cationic lipid DOTAP was evaluated by determining particle size distribution, encapsulation efficiency, the polydispersity index (PDI), and surface morphology. The cytotoxic effects of free Ginsenoside Rh2 and Ginsenoside Rh2-loaded niosomes were determined using the MTT method in the PC3 prostate cancer cell line. For the investigation of the in vitro cellular uptake of Ginsenoside Rh2-loaded niosome, two formulations were prepared: the Ginsenoside Rh2-loaded niosomal formula containing 5% DOTAP and the Ginsenoside Rh2-loaded niosomal formula without DOTAP.

          Results

          The mean size, DPI, zeta potential, and encapsulation efficiency of the Ginsenoside Rh2-loaded nanoniosomal formulation containing DOTAP were 93.5±2.1 nm, 0.203±0.01, +4.65±0.65, and 98.32% ±2.4, respectively. The niosomal vesicles were found to be round and have a smooth surface. The release profile of Ginsenoside Rh2 from niosome was biphasic. Furthermore, a two-fold reduction in the Ginsenoside Rh2 concentration was measured when Ginsenoside Rh2 was administered in a nanoniosomal form compared to free Ginsenoside Rh2 solutions in the PC3 prostate cancer cell line. After storage for 90 days, the encapsulation efficiency, vesicle size, PDI, and zeta potential of the optimized formulation did not significantly change compared to the freshly prepared samples. The cellular uptake experiments of the niosomal formulation demonstrated that by adding DOTAP to the niosomal formulation, the cellular uptake was enhanced.

          Discussion

          The enhanced cellular uptake and cytotoxic activity of the Ginsenoside Rh2 nanoniosomal formulation on the PC3 cell make it an attractive candidate for application as a nano-sized delivery vehicle to transfer Ginsenoside Rh2 to cancer cells.

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          Most cited references 41

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          Pharmacology of ginsenosides: a literature review

          The therapeutic potential of ginseng has been studied extensively, and ginsenosides, the active components of ginseng, are shown to be involved in modulating multiple physiological activities. This article will review the structure, systemic transformation and bioavailability of ginsenosides before illustration on how these molecules exert their functions via interactions with steroidal receptors. The multiple biological actions make ginsenosides as important resources for developing new modalities. Yet, low bioavailability of ginsenoside is one of the major hurdles needs to be overcome to advance its use in clinical settings.
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            Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure–Activity Relationships, and Molecular Mechanisms of Action

            Conventional chemotherapeutic agents are often toxic not only to tumor cells but also to normal cells, limiting their therapeutic use in the clinic. Novel natural product anticancer compounds present an attractive alternative to synthetic compounds, based on their favorable safety and efficacy profiles. Several pre-clinical and clinical studies have demonstrated the anticancer potential of Panax ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of ginseng is attributed mainly to the presence of saponins, known as ginsenosides. In this review, we focus on how ginsenosides exert their anticancer effects by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (c-myc, EGFR, and vascular endothelial growth factor), tumor suppressors (p53 and p21), oncogenes (MDM2), cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death receptors), inflammatory response molecules (NF-κB and COX-2), and protein kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the structure–activity relationship of various ginsenosides and their potentials in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further pre-clinical and clinical development of these agents for the treatment of primary and metastatic tumors.
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              Non-ionic surfactant based vesicles (niosomes) in drug delivery

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                13 August 2020
                2020
                : 14
                : 3315-3324
                Affiliations
                [1 ]Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences , Yazd, Iran
                [2 ]Department of Sciences, Farhangian University , Isfahan, Iran
                [3 ]Medical Nanotechnology &Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences , Yazd, Iran
                [4 ]Abadan Faculty of Medical Sciences , Abadan, Iran
                [5 ]Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan , Isfahan, Iran
                [6 ]Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                [7 ]Tissue Bank & Research Center, Tehran University of Medical Sciences , Tehran, Iran
                [8 ]Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University , Tehran, Iran
                [9 ]Stem Cell and Regenerative Medicine Institute, Tehran University of Medical Sciences , Tehran, Iran
                [10 ]Shoushtar Faculty of Medical Sciences, Shoushtar, Iran
                [11 ]Department of Pediatrics, Sabzevar University of Medical Sciences , Sabzevar, Iran
                [12 ]Kar Higher Education Institute of Rafsanjan , Rafsanjan, Iran
                Author notes
                Correspondence: Ashraf Alemi Tel/Fax +986153384008 Email alemi.ashraf@gmail.com
                Article
                261027
                10.2147/DDDT.S261027
                7431455
                © 2020 Zare-Zardini et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 0, References: 42, Pages: 10
                Categories
                Original Research

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