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首页> 外文期刊>International Journal of Pharmaceutics >Improvement of intestinal absorption of insulin and water-soluble macromolecular compounds by chitosan oligomers in rats.
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Improvement of intestinal absorption of insulin and water-soluble macromolecular compounds by chitosan oligomers in rats.

机译：壳聚糖低聚物改善大鼠肠道对胰岛素和水溶性高分子化合物的吸收。

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摘要

The effects of five chitosan oligomers on the intestinal absorption of fluorescein isothiocyanate-labeled dextrans (FDs) and insulin were studied by an in situ loop method. The absorption of FD4 from the jejunum was effectively improved in the presence of 0.5% (w/v) chitosan hexamer and dimer. However, chitosan hexamer did not improve the colonic absorption of FD4, although we found a moderate increase in the colonic absorption of FD4 in the presence of chitosan pentamer and dimer. The absorption enhancing effect of chitosan hexamer decreased as the molecular weights of FDs increased. In addition, we found a remarkable increase in plasma insulin levels and a significant hypoglycemic effect after jejunal administration of insulin with chitosan hexamer. In the toxicity studies of chitosan hexamer, we found no significant increase in the release of total protein and activity of lactate dehydrogenase (LDH) from the intestinal epithelium in the presence of chitosan hexamer (0.5%, w/v), indicating that this compound was a safe absorption enhancer for improving the intestinal absorption of poorly absorbable drugs. Finally, the transepithelial electrical resistance (TEER) and the permeability of FD4 in rat jejunal membranes with or without chitosan hexamer (0.5%, w/v) were examined by an in vitro diffusion chamber method. We observed a moderate decrease in the TEER values of rat jejunal membranes and a corresponding increase in the permeability of FD4 in the presence of chitosan hexamer (0.5%, w/v). These findings suggested that chitosan hexamer might loosen the tight junction of the intestinal epithelium, thereby improving the intestinal permeability of hydrophilic macromolecular compounds via a paracellular pathway.
机译：通过原位环法研究了五种壳聚糖低聚物对异硫氰酸荧光素标记的右旋糖酐（FDs）和胰岛素在肠道吸收的影响。在存在0.5％（w / v）的壳聚糖六聚体和二聚体的情况下，可有效提高空肠对FD4的吸收。然而，尽管我们发现在存在壳聚糖五聚体和二聚体的情况下，FD4的结肠吸收有适度增加，但是壳聚糖六聚体并没有改善FD4的结肠吸收。随着FDs分子量的增加，壳聚糖六聚体的吸收增强作用降低。此外，我们发现空肠给予壳聚糖六聚体胰岛素后，血浆胰岛素水平显着增加，降血糖作用显着。在壳聚糖六聚体的毒性研究中，我们发现在存在壳聚糖六聚体（0.5％，w / v）的情况下，总蛋白释放量和乳酸脱氢酶（LDH）从肠上皮的活性均未显着增加，表明该化合物是改善吸收不良的药物在肠道吸收的安全吸收促进剂。最后，通过体外扩散室方法检查了有或没有壳聚糖六聚体（0.5％，w / v）的大鼠空肠膜的跨上皮电阻（TEER）和FD4的渗透性。我们观察到，在存在壳聚糖六聚体的情况下，大鼠空肠膜的TEER值适度降低，而FD4的通透性相应增加（0.5％，w / v）。这些发现表明，壳聚糖六聚体可能会放松肠上皮的紧密连接，从而通过细胞旁途径改善亲水性大分子化合物的肠通透性。

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