Novel delivery system based on complexation hydrogels as delivery vehicles for insulin-transferrin conjugates
Novel delivery system based on complexation hydrogels as delivery vehicles for insulin-transferrin conjugates
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DOI：
10.1016/j.biomaterials.2006.02.026
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发表时间：
2006-07-01
期刊：
影响因子：
14
通讯作者：
Peppas, NA
中科院分区：
文献类型：
--
作者：
Kavimandan, NJ;Losi, E;Peppas, NA
已经研究了多种方法来解决与口服胰岛素递送相关的问题，但是口服胰岛素的生物利用度仍然很低。胰岛素在胃肠道中被酶迅速降解，不易通过上皮屏障转运。在这项工作中开发的口服胰岛素制剂利用络合水凝胶口服递送胰岛素生物缀合物。本工作合成的胰岛素生物缀合物由胰岛素与转铁蛋白分子结合组成，转铁蛋白分子可被上皮细胞摄取。偶联物可通过受体介导的转胞吞作用增加胰岛素穿过上皮屏障的渗透性。缀合物中的转铁蛋白也显示出在肠酶存在下稳定胰岛素。使用复合水凝胶递送胰岛素-转铁蛋白缀合物可以大大增加口服胰岛素的生物利用度。这是因为，已知络合水凝胶表现出使其成为口服蛋白质递送的理想候选物的特性。它们还可以抑制胰岛素在胃肠道中的降解。因此，这两种方法的组合可以提供用于口服胰岛素递送的创新平台。(c)2006爱思唯尔有限公司保留所有权利。
A variety of approaches have been investigated to address the problems associated with oral insulin delivery, but the bioavailability of oral insulin is still low. Insulin is rapidly degraded by the enzymes in the GI tract and is not transported across the epithelial barrier easily. The oral insulin formulation developed in this work makes use of complexation hydrogels for oral delivery of insulin bioconjugates. The insulin bioconjugates synthesized in this work consist of insulin bound to transferrin molecule which can be uptaken by the epithelial cells. The conjugates can increase the permeability of insulin across the epithelial barrier by receptor-mediated transcytosis. The transferrin in the conjugate is also shown to stabilize insulin in the presence of intestinal enzymes. Use of complexation hydrogels for delivery of insulin-transferrin conjugate may greatly increase the bioavailability of oral insulin. This is because, the complexation hydrogels are known to exhibit characteristics that make them ideal candidates for oral protein delivery. They can also inhibit the degradation of insulin in the GI tract. Thus, combination of these two approaches may provide an innovative platform for oral insulin delivery. (c) 2006 Elsevier Ltd. All rights reserved.