Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity
This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. M...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/7/652 |
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| author | Nabil A. Alhakamy Osama A. A. Ahmed Mallesh Kurakula Giuseppe Caruso Filippo Caraci Hani Z. Asfour Anas Alfarsi Basma G. Eid Amir I. Mohamed Nabil K. Alruwaili Wesam H. Abdulaal Usama A. Fahmy Hani A. Alhadrami Basmah M. Eldakhakhny Ashraf B. Abdel-Naim |
| author_facet | Nabil A. Alhakamy Osama A. A. Ahmed Mallesh Kurakula Giuseppe Caruso Filippo Caraci Hani Z. Asfour Anas Alfarsi Basma G. Eid Amir I. Mohamed Nabil K. Alruwaili Wesam H. Abdulaal Usama A. Fahmy Hani A. Alhadrami Basmah M. Eldakhakhny Ashraf B. Abdel-Naim |
| author_sort | Nabil A. Alhakamy |
| collection | DOAJ |
| description | This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA. |
| first_indexed | 2024-03-10T18:35:06Z |
| format | Article |
| id | doaj.art-f2115388129341d69a1e9e0585664d5c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T18:35:06Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f2115388129341d69a1e9e0585664d5c2023-11-20T06:18:52ZengMDPI AGPharmaceutics1999-49232020-07-0112765210.3390/pharmaceutics12070652Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic ActivityNabil A. Alhakamy0Osama A. A. Ahmed1Mallesh Kurakula2Giuseppe Caruso3Filippo Caraci4Hani Z. Asfour5Anas Alfarsi6Basma G. Eid7Amir I. Mohamed8Nabil K. Alruwaili9Wesam H. Abdulaal10Usama A. Fahmy11Hani A. Alhadrami12Basmah M. Eldakhakhny13Ashraf B. Abdel-Naim14Department 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 Biomedical Engineering, University of Memphis, Memphis, TN 38152, USAOasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina, ItalyOasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina, ItalyDepartment 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 Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Military Medical Academy, Cairo 11757, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Jouf University, Skaka, Al Jouf 2014, Saudi ArabiaDepartment of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi ArabiaDepartment of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaThis study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA.https://www.mdpi.com/1999-4923/12/7/652chitosanellagic aciddrug releasemuco-adhesioncolon targeting |
| spellingShingle | Nabil A. Alhakamy Osama A. A. Ahmed Mallesh Kurakula Giuseppe Caruso Filippo Caraci Hani Z. Asfour Anas Alfarsi Basma G. Eid Amir I. Mohamed Nabil K. Alruwaili Wesam H. Abdulaal Usama A. Fahmy Hani A. Alhadrami Basmah M. Eldakhakhny Ashraf B. Abdel-Naim Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity Pharmaceutics chitosan ellagic acid drug release muco-adhesion colon targeting |
| title | Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity |
| title_full | Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity |
| title_fullStr | Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity |
| title_full_unstemmed | Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity |
| title_short | Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity |
| title_sort | chitosan based microparticles enhance ellagic acid s colon targeting and proapoptotic activity |
| topic | chitosan ellagic acid drug release muco-adhesion colon targeting |
| url | https://www.mdpi.com/1999-4923/12/7/652 |
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