Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity
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
Affiliations
Nabil A. Alhakamy
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Osama A. A. Ahmed
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mallesh Kurakula
Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA
Giuseppe Caruso
Oasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina, Italy
Filippo Caraci
Oasi Research Institute—IRCCS, Via Conte Ruggero, 73, 94018 Troina, Italy
Hani Z. Asfour
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Anas Alfarsi
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Basma G. Eid
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Amir I. Mohamed
Department of Pharmaceutics and Industrial Pharmacy, Military Medical Academy, Cairo 11757, Egypt
Nabil K. Alruwaili
Department of Pharmaceutics, Faculty of Pharmacy, Jouf University, Skaka, Al Jouf 2014, Saudi Arabia
Wesam H. Abdulaal
Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Usama A. Fahmy
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Hani A. Alhadrami
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia
Basmah M. Eldakhakhny
Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Ashraf B. Abdel-Naim
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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.
