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Document Type |
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Thesis |
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Document Title |
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DESIGN AND EVALUATION OF COLON TARGETED DELIVERY SYSTEM OF TACROLIMUS تصميم وتقييم نظام لنقل التاكروليماس للقولون |
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Subject |
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Faculty of Medicine |
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Document Language |
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Arabic |
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Abstract |
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Inflammatory bowel disease (IBD) is chronic inflammation in the gastrointestinal tract which frequently associated with severe complications and often resists treatment. Tacrolimus (a potent immunosuppressant agent) has documented efficacy in the management of refractory cases, however, it has several serious side effects which limits its use. This background facilitated the motivation for the current project. Colon targeted delivery system (CTDS) of FK506 was successfully prepared using Eudragit S100 (ED) adopting a simple pharmaceutical technique (solvent evaporation emulsion technique). Microspheres were prepared using drug: polymer ratio of 1:5 which provided favorable pharmaceutical characteristics, including high stability, uniform size, good surface morphology adequate entrapment efficiency (by HPLC), and effectively retarded drug dissolution which likely to provide at least 60 % release in the colon. These formulae were tested in an animal model for colitis to study drug efficacy. Dextran sodium sulfate (DSS 5 % w/w) was given by oral gavage to induce acute colitis in Wister rats for 6 days. This modification insures less variability among animal in colitis severity. Sulfasalazine in a maximum tolerated dose (500 mg/ kg) was used as the positive control. CTDS FK506 (was given by oral gavage) in doses equivalent to 1-3 mg/kg, for 5 days. Colon tissues were taken to determine proinflammatory tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), by ELISA. Blood samples were taken to determine, serum trough level of FK506. A histopathological study of the colon was done by conventional H&E staining and morphometric analysis. The results showed that (TNF-α, IL-1β, and IL-6) were markedly raised in distal colon tissues of rats with DSS induced colitis. Many histopathological changes in addition to atrophy of their lining epithelium were observed. FK506 CTDS in all doses significantly normalize all immunological and histological changes.
The study confirmed the efficacy of FK506 CTDS in management of DSS induced colitis. The study recommends further work on FK506 for optimizing the pharmaceutic formulation, pharmacokinetic studies and safety studies. |
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Supervisor |
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Dr. Ahmed Shaker Ali |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1440 AH
2019 AD |
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Added Date |
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Tuesday, July 16, 2019 |
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Researchers
| عابد عبدالله الطياري | ALTAYARI, ABID ABDULLAH | Researcher | Master | |
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