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      Preparation and Characterization of PEG-PLA Genistein Micelles Using a Modified Emulsion-Evaporation Method

      Author(s): 1 , 2 , 3 , 2 , 1 , 1 , 1 , 4
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      Publication date Created:
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      Journal: Journal of Nanomaterials
      Publisher: Hindawi Limited

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          Abstract

          The objective of this study is to improve the bioavailability of genistein by encapsulation with polyethylene glycol-polylactic acid (PEG-PLA) copolymers. Genistein micelles (GMs) prepared using a modified emulsion-evaporation method were more stable than those made with the original method. The effect of polyvinyl alcohol, Tween 80, sonication time, PEG-PLA/genistein ratio, and organic phase (acetone)/H2O ratio on the size, polydispersity index, encapsulation efficiency, and drug loading efficiency of GMs was investigated. GMs were obtained and characterized under optimal experimental conditions. For long-term storage, GMs were lyophilized by freeze drying with trehalose to produce genistein lyophilized powder (GLP). The analysis of GLP by Fourier-transform infrared spectroscopy and differential scanning calorimetry showed that genistein was successfully incorporated into the micellar structure. In vitro release experiments revealed that the incorporation of genistein into PEG-PLA copolymers significantly improved its solubility and bioavailability. GLP was more potent in inhibiting the proliferation of HSC-T6 cells than genistein. Treatment with GLP at 10–20 μg/mL for 48 h significantly inhibited the protein expression of α-smooth muscle actin and collagen I in HSC-T6 cells compared with the control. These data demonstrated that the improved solubility and bioavailability of genistein in the form of GLP enhanced its antifibrotic effect in vitro.

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          Hepatic stellate cells as key target in liver fibrosis.

          Takaaki Higashi, Scott Friedman, Yujin Hoshida (2017)
          Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
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            Senescence of activated stellate cells limits liver fibrosis.

            Valery Krizhanovsky, Monica Yon, Ross A Dickins … (2008)
            Cellular senescence acts as a potent mechanism of tumor suppression; however, its functional contribution to noncancer pathologies has not been examined. Here we show that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis. The senescent cells are derived primarily from activated hepatic stellate cells, which initially proliferate in response to liver damage and produce the extracellular matrix deposited in the fibrotic scar. In mice lacking key senescence regulators, stellate cells continue to proliferate, leading to excessive liver fibrosis. Furthermore, senescent activated stellate cells exhibit gene expression profile consistent with cell-cycle exit, reduced secretion of extracellular matrix components, enhanced secretion of extracellular matrix-degrading enzymes, and enhanced immune surveillance. Accordingly natural killer cells preferentially kill senescent activated stellate cells in vitro and in vivo, thereby facilitating the resolution of fibrosis. Therefore, the senescence program limits the fibrogenic response to acute tissue damage.
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              Genistein and cancer: current status, challenges, and future directions.

              Carmela Spagnuolo, Gian Russo, Ilkay Orhan … (2015)
              Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.
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                Author and article information

                Contributors
                Journal
                Title: Journal of Nanomaterials
                Abbreviated Title: Journal of Nanomaterials
                Publisher: Hindawi Limited
                ISSN (Electronic): 1687-4129
                ISSN (Print): 1687-4110
                Publication date Created: November 1 2020
                Publication date (Print): November 1 2020
                Volume: 2020
                Pages: 1-15
                Affiliations
                [1 ]Department of Infectious Diseases, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi 530021, China
                [2 ]Guangxi Botanical Garden of Medicinal Plants, No. 189 Changgang Road, Nanning, Guangxi 530021, China
                [3 ]College of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue East Road, Nanning, 530004 Guangxi, China
                [4 ]Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi 530021, China
                Article
                DOI: 10.1155/2020/3278098
                SO-VID: 702a4656-59f7-4b3a-a1c5-a0460aa33d36
                Copyright © © 2020
                License:

                https://creativecommons.org/licenses/by/4.0/

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