Association of tumor necrosis factor-α and -ß gene polymorphisms in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case-control study was to evaluate the association of tumor necrosis factor-alpha (TNF-α) (308) and -ß (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn's disease (CD) =95) and 200 age- and sex-matched healthy controls were recruited. TNF-α and TNF-ß genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-α (-308) and -ß (+252) polymorphisms. The frequency of the GA genotype of TNF-α (-308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-α (-308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-ß (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-ß was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-α and-ß polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-α (-308G/A) and TNF-ß (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.

New targeted-colon delivery system: in vitro and in vivo evaluation using X-ray imaging.

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.

Mucoadhesive polymeric hydrogels for nasal delivery of acyclovir.

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.