Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation
Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation
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DOI：
10.1016/j.ejpb.2015.01.014
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发表时间：
2015-09-01
影响因子：
4.9
通讯作者：
Nielsen, Hanne Morck
中科院分区：
文献类型：
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作者：
Boegh, Marie;Garcia-Diaz, Maria;Nielsen, Hanne Morck
胃肠道上皮的粘液衬里被认为是有效口服药物递送的屏障。最近，通过将生物仿制药粘液基质应用于Caco-2细胞单层表面，建立了一种新的用于评估药物穿过肠粘膜渗透的体外模型。本研究的目的是通过研究肽和模型化合物穿过生物仿制药粘液以及穿过猪肠粘液（PIM）的渗透，更深入地了解肠粘液的空间和相互作用屏障特性。由于PIM破坏了Caco-2细胞单层，因此在研究中实施了无细胞粘液屏障模型。生物仿制药粘液和PIM都在不同程度上降低了所选肽药物的渗透，说明了两种粘液基质的相互作用性质。肽渗透的减少取决于渗透物的阳离子性和H-键合能力，通过使用生物仿制药粘液清楚地证明了这一点，而PIM基质的较大样品间变化阻碍了类似的明确结论。因此，对于跨粘液和粘膜渗透的机制研究，生物仿制药粘液提供了天然粘液的相关且可重现的替代方案。(C)2015爱思唯尔B. V.保留所有权利。
The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus. (C) 2015 Elsevier B.V. All rights reserved.