Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells
Icariin (ICA) is a flavonol glycoside that has pleiotropic pharmacological actions. It has cytotoxic effects against ovarian cancer cells and increases their chemosensitivity to chemotherapeutic drugs. Phytosomes are identified for their potential in drug delivery of cytotoxic agents. Thus, the purp...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/4/346 |
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| author | Nabil A. Alhakamy Usama A. Fahmy Shaimaa M. Badr-Eldin Osama A. A. Ahmed Hani Z. Asfour Hibah M. Aldawsari Mardi M. Algandaby Basma G. Eid Ashraf B. Abdel-Naim Zuhier A. Awan Nabil K. Alruwaili Amir I. Mohamed |
| author_facet | Nabil A. Alhakamy Usama A. Fahmy Shaimaa M. Badr-Eldin Osama A. A. Ahmed Hani Z. Asfour Hibah M. Aldawsari Mardi M. Algandaby Basma G. Eid Ashraf B. Abdel-Naim Zuhier A. Awan Nabil K. Alruwaili Amir I. Mohamed |
| author_sort | Nabil A. Alhakamy |
| collection | DOAJ |
| description | Icariin (ICA) is a flavonol glycoside that has pleiotropic pharmacological actions. It has cytotoxic effects against ovarian cancer cells and increases their chemosensitivity to chemotherapeutic drugs. Phytosomes are identified for their potential in drug delivery of cytotoxic agents. Thus, the purpose of this study was to determine the potential enhancement of ICA cytotoxicity activity in OVCAR-3 ovarian cancer cells via its formulation in phytosomes. ICA-phytosomal formulation was optimized using a Box–Behnken design. Particle size, shape, and in vitro drug release were used to characterize the optimized formula. The optimized formulation exhibited enhanced in vitro drug release. ICA-phytosomes exhibited enhanced cytotoxicity against ovarian cancer cells. Cell cycle analysis indicated accumulation of cells challenged with ICA-phytosomes in G2/M and pre-G1 phases. Staining of cells with annexin V indicated significant elevation of percentage cells with early and late apoptosis as well as total cell death. In addition, the formulation significantly disturbed mitochondrial membrane potential and cellular content of caspase 3. In addition, intracellular release of reactive oxygen species (ROS) was enhanced by ICA-phytosomes. In conclusion, phytosome formulation of ICA significantly potentiates its cytotoxic activities against OVCAR-3 cells. This is mediated, at least partly, by enhanced ICA cellular permeation, apoptosis, and ROS. |
| first_indexed | 2024-03-10T20:32:00Z |
| format | Article |
| id | doaj.art-804007c971b64a8582a1ca169d96a485 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:32:00Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-804007c971b64a8582a1ca169d96a4852023-11-19T21:20:49ZengMDPI AGPharmaceutics1999-49232020-04-0112434610.3390/pharmaceutics12040346Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer CellsNabil A. Alhakamy0Usama A. Fahmy1Shaimaa M. Badr-Eldin2Osama A. A. Ahmed3Hani Z. Asfour4Hibah M. Aldawsari5Mardi M. Algandaby6Basma G. Eid7Ashraf B. Abdel-Naim8Zuhier A. Awan9Nabil K. Alruwaili10Amir I. Mohamed11Department 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 Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21579, 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 Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, Jouf University, Skaka 2014, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Military Medical Academy, Cairo 11757, EgyptIcariin (ICA) is a flavonol glycoside that has pleiotropic pharmacological actions. It has cytotoxic effects against ovarian cancer cells and increases their chemosensitivity to chemotherapeutic drugs. Phytosomes are identified for their potential in drug delivery of cytotoxic agents. Thus, the purpose of this study was to determine the potential enhancement of ICA cytotoxicity activity in OVCAR-3 ovarian cancer cells via its formulation in phytosomes. ICA-phytosomal formulation was optimized using a Box–Behnken design. Particle size, shape, and in vitro drug release were used to characterize the optimized formula. The optimized formulation exhibited enhanced in vitro drug release. ICA-phytosomes exhibited enhanced cytotoxicity against ovarian cancer cells. Cell cycle analysis indicated accumulation of cells challenged with ICA-phytosomes in G2/M and pre-G1 phases. Staining of cells with annexin V indicated significant elevation of percentage cells with early and late apoptosis as well as total cell death. In addition, the formulation significantly disturbed mitochondrial membrane potential and cellular content of caspase 3. In addition, intracellular release of reactive oxygen species (ROS) was enhanced by ICA-phytosomes. In conclusion, phytosome formulation of ICA significantly potentiates its cytotoxic activities against OVCAR-3 cells. This is mediated, at least partly, by enhanced ICA cellular permeation, apoptosis, and ROS.https://www.mdpi.com/1999-4923/12/4/346apoptosiscaspaseicariinphytosomesreactive oxygen species |
| spellingShingle | Nabil A. Alhakamy Usama A. Fahmy Shaimaa M. Badr-Eldin Osama A. A. Ahmed Hani Z. Asfour Hibah M. Aldawsari Mardi M. Algandaby Basma G. Eid Ashraf B. Abdel-Naim Zuhier A. Awan Nabil K. Alruwaili Amir I. Mohamed Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells Pharmaceutics apoptosis caspase icariin phytosomes reactive oxygen species |
| title | Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells |
| title_full | Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells |
| title_fullStr | Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells |
| title_full_unstemmed | Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells |
| title_short | Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells |
| title_sort | optimized icariin phytosomes exhibit enhanced cytotoxicity and apoptosis inducing activities in ovarian cancer cells |
| topic | apoptosis caspase icariin phytosomes reactive oxygen species |
| url | https://www.mdpi.com/1999-4923/12/4/346 |
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