The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells
Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-lab...
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MDPI AG
2020-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/10/956 |
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| author | Usama A. Fahmy Hibah M. Aldawsari Shaimaa M. Badr-Eldin Osama A. A. Ahmed Nabil A. Alhakamy Helal H. Alsulimani Filippo Caraci Giuseppe Caruso |
| author_facet | Usama A. Fahmy Hibah M. Aldawsari Shaimaa M. Badr-Eldin Osama A. A. Ahmed Nabil A. Alhakamy Helal H. Alsulimani Filippo Caraci Giuseppe Caruso |
| author_sort | Usama A. Fahmy |
| collection | DOAJ |
| description | Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells. |
| first_indexed | 2024-03-10T15:43:29Z |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T15:43:29Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7a271cccb0a64316804ea6234f8690ed2023-11-20T16:37:16ZengMDPI AGPharmaceutics1999-49232020-10-01121095610.3390/pharmaceutics12100956The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer CellsUsama A. Fahmy0Hibah M. Aldawsari1Shaimaa M. Badr-Eldin2Osama A. A. Ahmed3Nabil A. Alhakamy4Helal H. Alsulimani5Filippo Caraci6Giuseppe Caruso7Department 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 ArabiaOasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina (EN), ItalyOasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina (EN), ItalyFebuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.https://www.mdpi.com/1999-4923/12/10/956febuxostatemulsomesdrug releaseapoptosisnecrosiscytotoxicity |
| spellingShingle | Usama A. Fahmy Hibah M. Aldawsari Shaimaa M. Badr-Eldin Osama A. A. Ahmed Nabil A. Alhakamy Helal H. Alsulimani Filippo Caraci Giuseppe Caruso The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells Pharmaceutics febuxostat emulsomes drug release apoptosis necrosis cytotoxicity |
| title | The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells |
| title_full | The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells |
| title_fullStr | The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells |
| title_full_unstemmed | The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells |
| title_short | The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells |
| title_sort | encapsulation of febuxostat into emulsomes strongly enhances the cytotoxic potential of the drug on hct 116 colon cancer cells |
| topic | febuxostat emulsomes drug release apoptosis necrosis cytotoxicity |
| url | https://www.mdpi.com/1999-4923/12/10/956 |
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