Food-associated stimuli enhance barrier properties of gastrointestinal mucus.
Food-associated stimuli enhance barrier properties of gastrointestinal mucus.
复制标题
食物相关的刺激增强了胃肠道粘液的屏障特性。
DOI：
10.1016/j.biomaterials.2015.02.118
复制
发表时间：
2015-06
期刊：
影响因子：
14
通讯作者：
Carrier, Rebecca L.
中科院分区：
文献类型：
--
作者：
Yildiz, Hasan M.;Speciner, Lauren;Ozdemir, Cafer;Cohen, David E.;Carrier, Rebecca L.
口服给药的药物和营养物质必须通过黏液扩散才能进入循环系统，但黏液的屏障特性及其受生理因素的调节通常知之甚少。本研究的主要目的是研究食物摄入时发生的物理化学变化对胃肠道粘液屏障特性的影响。代表餐后肠道内容物的脂质增强了粘液屏障，表明200纳米微球通过粘液的运输速率降低了10 - 142倍，这取决于表面化学。生理上相关的[Ca2+]增加导致运输速率降低2 - 4倍，可能是由于粘液凝胶网络的交联增强。pH值从6.5降至3.5也会影响黏液的粘弹性，使颗粒传输速率降低约5 - 10倍。宏观目视观察和微尺度凝集素染色显示黏液凝胶结构改变，包括聚集成颗粒未穿透的区域。组织学检查表明，食物摄入可阻止微球与肠上皮的接触和内吞作用。综上所述，这些结果表明，与进食和脂基输送系统的潜在剂量相关的刺激显著改变了胃肠道粘液屏障；这些刺激代表了在设计口腔疗法时需要考虑的广泛相关的变量。
Orally delivered drugs and nutrients must diffuse through mucus to enter the circulatory system, but the barrier properties of mucus and their modulation by physiological factors are generally poorly characterized. The main objective of this study was to examine the impact of physicochemical changes occurring upon food ingestion on gastrointestinal (GI) mucus barrier properties. Lipids representative of postprandial intestinal contents enhanced mucus barriers, as indicated by a 10 – 142-fold reduction in the transport rate of 200 nm microspheres through mucus, depending on surface chemistry. Physiologically relevant increases in [Ca2+] resulted in a 2 - 4-fold reduction of transport rates, likely due to enhanced cross-linking of the mucus gel network. Reduction of pH from 6.5 to 3.5 also affected mucus viscoelasticity, reducing particle transport rates approximately 5 – 10-fold. Macroscopic visual observation and micro-scale lectin staining revealed mucus gel structural changes, including clumping into regions into which particles did not penetrate. Histological examination indicated food ingestion can prevent microsphere contact with and endocytosis by intestinal epithelium. Taken together, these results demonstrate that GI mucus barriers are significantly altered by stimuli associated with eating and potentially dosing of lipid-based delivery systems; these stimuli represent broadly relevant variables to consider upon designing oral therapies.
登录
查看更多内容
影响因子：
16.1
作者：
Lai, Samuel K.;Wang, Ying-Ying;Hanes, Justin
通讯作者：
Hanes, Justin
DOI：
10.1152/ajpgi.2001.280.5.g922
发表时间：
2001-05-01
影响因子：
4.5
作者：
Atuma, C;Strugala, V;Holm, L
通讯作者：
Holm, L
影响因子：
3.7
作者：
Buyukozturk, Fulden;Di Maio, Selena;Carrier, Rebecca L.
通讯作者：
Carrier, Rebecca L.
影响因子：
3.1
作者：
GIROD, S;GALABERT, C;PUCHELLE, E
通讯作者：
PUCHELLE, E
影响因子：
6
作者：
Jordan, N;Newton, J;Allen, A
通讯作者：
Allen, A