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Polyvinyl Alcohol (Pva)-Based Nanoniosome for Enhanced in Vitro Delivery and Anticancer Activity of Thymol Publisher Pubmed



Abdihaji M1 ; Chegeni MM2 ; Hadizadeh A3 ; Farrokhzad N4 ; Kheradmand Z5 ; Fakhrfatemi P6 ; Faress F7 ; Moeinabadibidgoli K8 ; Noorbazargan H9 ; Mostafavi E10, 11
Authors
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Authors Affiliations
  1. 1. Department of Biology, The Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN, United States
  2. 2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  3. 3. Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Medicine and Health, University of Manchester, Manchester, United Kingdom
  5. 5. Department of Agriculture, Islamic Azad University Maragheh Branch, Maragheh, Iran
  6. 6. Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Department of Business, Data Analysis, The University of Texas Rio Grande Valley (UTRGV), Edinburg, TX, United States
  8. 8. Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  9. 9. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  10. 10. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
  11. 11. Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States

Source: International Journal of Nanomedicine Published:2023


Abstract

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells. © 2023 Abdihaji et al.
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