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Abstract
The aim of this study was to formulate a new orally-administered colon delivery system of 5-flurouracil (5-FU) for the treatment of colon cancer. The system was designed to target 5-FU directly to the colon with high potential of much more effective and less toxic colon cancer treatment. The system was prepared by compression coating technique using granulated chitosan. The method was optimized by studying the effect of granulation and thickness of the coat with respect to the in vitro performance in a medium mimicking mouth-to-colon environment. The in vivo selectivity of the system was assessed by X-ray imaging technique using beagle dogs. Results showed that granulation of chitosan were effective in protecting against the known acid solubility of the polymer. Formula (F7) with coat weight of 50 mg/tablet exhibited the best protection profile with <10% of the drug released after 6 h. The resistance of the system to the simulated gastro-intestinal media was reduced as the chitosan coat weight decreases. The performance of the system in a rat caecal contents containing-medium showed that the susceptibility of this system for the enzymatic degradation by colonic enzymes. The X-ray imaging gave rise to the in vivo selectivity of this system for colon targeting by showing the resistivity of the system to the stomach and small intestine environment and the selective disintegration of the system inside the large bowel.
Acknowledgments
The authors would like to thank Mr. Saleh Al-Harby and Mr. Bandar Almahammed, Center for Laboratory Animals and Experimental Surgery, College of Medicine for their help with the experimental animals. We are also indebted to Mr. Michael Sehimde Giwa who contributed to the successful completion of this project. The gratitude is also extended to the College of Medicine for providing the facilities to carry out this study. The authors gratefully acknowledge the generous financial support by King Abdulaziz City for Science and Technology (Grant No. AT-25-23).
Declaration of interest: The authors report no conflicts of interest. The authors alone are resposible for the content and writing of this paper.