An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease
An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease
复制标题
一种口服核苷酸递送载体，靶向结肠巨噬细胞，用于治疗炎症性肠病。
DOI：
10.1016/j.biomaterials.2015.01.013
复制
发表时间：
2015-04-01
期刊：
影响因子：
14
通讯作者：
Dong, Lei
中科院分区：
文献类型：
--
作者：
Huang, Zhen;Gan, Jingjing;Dong, Lei
肿瘤坏死因子-α(TNF-α)在炎症性肠病(IBD)发病机制中起核心作用。抗肿瘤坏死因子-α疗法已显示出对结肠炎的保护作用，但仍迫切需要一种有效的工具来靶向抑制其分泌--最好是通过口服给药。在结肠组织中，肿瘤坏死因子-α主要由结肠巨噬细胞分泌。在这里，我们报告了一种口服微球载体，它可以靶向结肠巨噬细胞并抑制局部肿瘤坏死因子-α的表达，用于IBD的治疗。这种载体是由阳离子魔芋葡甘聚糖(CKGM)、植胶和针对肿瘤坏死因子-α的反义寡核苷酸组成的。给葡聚糖硫酸钠(DSS)结肠炎小鼠灌胃给药。CKGM独特的溶胀特性使cKGM-反义核苷酸(ASO)纳米复合体从植入物支架自发释放到结肠腔，ASO通过受体介导的吞噬作用转移到结肠巨噬细胞。治疗可明显降低局部肿瘤坏死因子-α水平，减轻小鼠结肠炎症状。综上所述，我们的研究证明了一种方便的口服给药系统，可以有效地靶向结肠巨噬细胞抑制肿瘤坏死因子-α的表达。它可能是治疗IBD的一种很有前途的治疗方法。(C)2015爱思唯尔有限公司。保留所有权利。
Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF-alpha therapies have shown protective effects against colitis, but an efficient tool for target suppression of its secretion - ideally via oral administration - remains in urgent demand. In the colon tissue, TNF-alpha is mainly secreted by the colonic macrophages. Here, we report an orally-administrated microspheric vehicle that can target the colonic macrophages and suppress the local expression of TNF-alpha for IBD treatment. This vehicle is formed by cationic konjac glucomannan (cKGM), phytagel and an antisense oligonucleotide against TNF-alpha. It was given to dextran sodium sulfate (DSS) colitic mice via gastric perfusion. The unique swelling properties of cKGM enabled the spontaneous release of cKGM& antisense nucleotide (ASO) nano-complex from the phytagel scaffold into the colon lumen, where the ASO was transferred into colonic macrophages via receptor-mediated phagocytosis. The treatment significantly decreased the local level of TNF-alpha and alleviated the symptoms of colitis in the mice. In summary, our study demonstrates a convenient, orally-administrated drug delivery system that effectively targets colonic macrophages for suppression of TNF-alpha expression. It may represent a promising therapeutic approach in the treatment of IBD. (C) 2015 Elsevier Ltd. All rights reserved.