betadex and Inflammatory-Bowel-Diseases

Surface-deacetylated chitin nanofibers (SDACNFs) reinforced with a sulfobutyl ether β-cyclodextrin (SBE-β-CD) (NFs-CDs) gel were developed to obtain a controlled release carrier of prednisolone (PD) for the treatment of colitis. PD was released slowly from the gel at both pH 1.2 and 6.8. The in vitro slow release of PD from the NFs-CDs gel was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple gel composed of a mixture of SDACNFs and SBE-β-CD has the potential for use in the controlled release of PD. We also evaluated the therapeutic effects of the NFs-CDs gel containing PD on dextran sulfate sodium (DSS)-induced colitis model mice. The administration of the NFs-CDs gel at intervals of 3days from the beginning of the DSS treatment resulted in a significant improvement, not only in colitis symptoms but also histopathological changes in colon tissue. In addition, the therapeutic effects of the NFs-CDs gel on colitis can be attributed to decreased levels of neutrophil infiltration and the development of oxidative stress. These efficacy profiles of the NFs-CDs gel containing PD suggest that it has the potential for use in the treatment of, not only colitis, but also a variety of other disorders associated with inflammation and oxidative injuries.

Topics: Animals; beta-Cyclodextrins; Chitin; Colitis; Delayed-Action Preparations; Dextran Sulfate; Gels; Inflammatory Bowel Diseases; Male; Mice; Mice, Inbred ICR; Nanofibers; Prednisolone; Rats; Rats, Wistar; Solubility

The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with beta-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/beta-CD or AUR/beta-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/beta-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 +/- 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/beta-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/beta-CD and AUR/beta-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-alpha, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1beta, which were induced in the adenocarcinomas. Our findings indicate that GOFA/beta-CD and AUR/beta-CD, especially GOFA/beta-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.

Topics: Animals; beta-Cyclodextrins; Colonic Neoplasms; Colorectal Neoplasms; Coumarins; Diterpenes; Humans; Immunohistochemistry; Incidence; Inflammation; Inflammatory Bowel Diseases; Inhibitor of Apoptosis Proteins; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred ICR; Microtubule-Associated Proteins; NF-kappa B; Proliferating Cell Nuclear Antigen; Propionates; Repressor Proteins; Survivin; Tumor Necrosis Factor-alpha

To investigate a possible increase of basolateral expression of carcinoembryonic antigen (CEA) by interfering with the apical transport machinery, we studied the effect of cholesterol depletion on CEA sorting and secretion.. Cholesterol depletion was performed in polarized Caco-2 cells using lovastatin and methyl-beta-cyclodextrin.. We show that CEA is predominantly expressed and secreted at the apical surface. Reduction of the cholesterol level of the cell by 40%-50% with lovastatin and methyl-beta-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.. As basolateral expression of CEA has been suggested to have anti-inflamatory properties, Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

Topics: Adenocarcinoma; Anticholesteremic Agents; beta-Cyclodextrins; Biological Transport; Caco-2 Cells; Carcinoembryonic Antigen; Cell Line, Tumor; Cell Membrane; Cholesterol; Colonic Neoplasms; Humans; Inflammatory Bowel Diseases; Lovastatin