Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells
Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells’ penetration and achieving better tumor-targeted delivery of active ingredients. Therefore,...
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MDPI AG
2022-08-01
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| author | Shaimaa M. Badr-Eldin Hibah M. Aldawsari Usama A. Fahmy Osama A. A. Ahmed Nabil A. Alhakamy Omar D. Al-hejaili Alhanoof A. Alhassan Ghadeer A. Ammari Shouq I. Alhazmi Raghad M. Alawadi Rana Bakhaidar Abdulmohsen J. Alamoudi Thikryat Neamatallah Singkome Tima |
| author_facet | Shaimaa M. Badr-Eldin Hibah M. Aldawsari Usama A. Fahmy Osama A. A. Ahmed Nabil A. Alhakamy Omar D. Al-hejaili Alhanoof A. Alhassan Ghadeer A. Ammari Shouq I. Alhazmi Raghad M. Alawadi Rana Bakhaidar Abdulmohsen J. Alamoudi Thikryat Neamatallah Singkome Tima |
| author_sort | Shaimaa M. Badr-Eldin |
| collection | DOAJ |
| description | Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells’ penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon<sup>®</sup> 90 G: cholesterol molar ratio (PC: CH; X<sub>1</sub>, mole/mole), Phospholipon<sup>®</sup> 90 G: Tristearin weight ratio (PC: TS; X<sub>2</sub>, <i>w</i>/<i>w</i>) and apamin molar concentration (APA conc.; X<sub>3</sub>, mM) were considered as independent variables, while vesicle size (VS, Y<sub>1</sub>, nm) and zeta potential (ZP, Y<sub>2</sub>, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC<sub>50</sub> value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of <i>p53, bax</i> and <i>casp3</i> and downregulating <i>bcl2</i>. Furthermore, NF-κB activity was abolished while the expression of <i>TNfα</i> was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation. |
| first_indexed | 2024-03-09T13:14:36Z |
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| spelling | doaj.art-72da4864ba9e40508d7eaf23ff29fc0e2023-11-30T21:37:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316944010.3390/ijms23169440Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer CellsShaimaa M. Badr-Eldin0Hibah M. Aldawsari1Usama A. Fahmy2Osama A. A. Ahmed3Nabil A. Alhakamy4Omar D. Al-hejaili5Alhanoof A. Alhassan6Ghadeer A. Ammari7Shouq I. Alhazmi8Raghad M. Alawadi9Rana Bakhaidar10Abdulmohsen J. Alamoudi11Thikryat Neamatallah12Singkome Tima13Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandEllagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells’ penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon<sup>®</sup> 90 G: cholesterol molar ratio (PC: CH; X<sub>1</sub>, mole/mole), Phospholipon<sup>®</sup> 90 G: Tristearin weight ratio (PC: TS; X<sub>2</sub>, <i>w</i>/<i>w</i>) and apamin molar concentration (APA conc.; X<sub>3</sub>, mM) were considered as independent variables, while vesicle size (VS, Y<sub>1</sub>, nm) and zeta potential (ZP, Y<sub>2</sub>, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC<sub>50</sub> value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of <i>p53, bax</i> and <i>casp3</i> and downregulating <i>bcl2</i>. Furthermore, NF-κB activity was abolished while the expression of <i>TNfα</i> was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation.https://www.mdpi.com/1422-0067/23/16/9440nanotechnologyphospholipontristearinapaminemulsomesellagic acid |
| spellingShingle | Shaimaa M. Badr-Eldin Hibah M. Aldawsari Usama A. Fahmy Osama A. A. Ahmed Nabil A. Alhakamy Omar D. Al-hejaili Alhanoof A. Alhassan Ghadeer A. Ammari Shouq I. Alhazmi Raghad M. Alawadi Rana Bakhaidar Abdulmohsen J. Alamoudi Thikryat Neamatallah Singkome Tima Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells International Journal of Molecular Sciences nanotechnology phospholipon tristearin apamin emulsomes ellagic acid |
| title | Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells |
| title_full | Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells |
| title_fullStr | Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells |
| title_full_unstemmed | Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells |
| title_short | Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells |
| title_sort | optimized apamin mediated nano lipidic carrier potentially enhances the cytotoxicity of ellagic acid against human breast cancer cells |
| topic | nanotechnology phospholipon tristearin apamin emulsomes ellagic acid |
| url | https://www.mdpi.com/1422-0067/23/16/9440 |
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