Boegh Marie, García-Díaz María, Müllertz Anette, Nielsen Hanne Mørck
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen O, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen O, Denmark.
Eur J Pharm Biopharm. 2015 Sep;95(Pt A):136-43. doi: 10.1016/j.ejpb.2015.01.014. Epub 2015 Jan 23.
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.
胃肠道上皮的黏液层被认为是高效口服给药的一个屏障。最近，通过将生物相似性黏液基质应用于Caco-2细胞单层表面，建立了一种用于评估药物跨肠黏膜渗透的新体外模型。本研究的目的是通过研究肽和模型化合物在生物相似性黏液以及猪肠黏液（PIM）中的渗透情况，更深入地了解肠黏液的空间位阻和相互作用屏障特性。由于PIM会破坏Caco-2细胞单层，因此在研究中采用了无细胞黏液屏障模型。生物相似性黏液和PIM均不同程度地降低了所选肽类药物的渗透，这说明了两种黏液基质的相互作用特性。通过使用生物相似性黏液清楚地表明，肽渗透的降低程度取决于渗透物的阳离子性和氢键结合能力，而PIM基质较大的样本间差异阻碍了得出同样明确的结论。因此，对于跨黏液和黏膜渗透的机制研究，生物相似性黏液为天然黏液提供了一种相关且可重复的替代物。
