Sjögren Erik, Eriksson Johanna, Vedin Charlotta, Breitholtz Katarina, Hilgendorf Constanze
Department of Pharmacy, Uppsala University, Uppsala 75233, Sweden.
Department of Pharmacy, Uppsala University, Uppsala 75233, Sweden.
Int J Pharm. 2016 May 30;505(1-2):361-8. doi: 10.1016/j.ijpharm.2016.03.063. Epub 2016 Apr 9.
Excised rat intestinal tissue mounted in an Ussing chamber can be used for intestinal permeability assessments in drug development. The outer layer of the intestine, the serosa and part of the muscle layer, is traditionally removed since it is considered a barrier to the diffusion of nutrients and oxygen as well as to that of pharmaceutical substances. However, the procedure for removing the serosal-muscle layer, i.e. stripping, is a technically challenging process in the pre-experimental preparation of the tissue which may result in tissue damage and reduced viability of the segment. In this study, the viability of stripped and native (non-stripped) rat small intestine tissue segments mounted in Ussing chambers was monitored and the apparent permeability of the tissue to a set of test compounds across both tissue preparations was determined. Electrical measurements, in particular the potential difference (PD) across the intestinal membrane, were used to evaluate the viability. In this study, there were no differences in initial PD (health status of the tissue) or PD over time (viability throughout the experiment) between native and stripped rat jejunum segments. Overall, there were also no significant differences in permeability between stripped and native rat intestinal tissue for the compounds in this study. Based on these results, we propose that stripping can be excluded from the preparation procedures for rat jejunal tissue for permeability studies when using the Ussing chamber technique.
安装在尤斯灌流室中的切除大鼠肠道组织可用于药物开发中的肠道通透性评估。传统上,肠道外层的浆膜和部分肌肉层会被去除,因为它被认为是营养物质和氧气扩散以及药物物质扩散的屏障。然而,去除浆膜 - 肌肉层的过程,即剥离,在组织的实验前准备中是一个技术上具有挑战性的过程,这可能会导致组织损伤和片段活力降低。在本研究中,监测了安装在尤斯灌流室中的剥离和天然(未剥离)大鼠小肠组织片段的活力,并测定了两组组织制剂对一组测试化合物的表观通透性。通过电学测量,特别是跨肠膜的电位差(PD)来评估活力。在本研究中,天然和剥离的大鼠空肠段之间在初始PD(组织健康状态)或随时间的PD(整个实验过程中的活力)方面没有差异。总体而言,对于本研究中的化合物,剥离和天然大鼠肠道组织之间的通透性也没有显著差异。基于这些结果,我们建议在使用尤斯灌流室技术进行通透性研究时,大鼠空肠组织的制备程序中可以排除剥离步骤。