The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23, Uppsala, Sweden.
The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23, Uppsala, Sweden; The Swedish Drug Delivery Center, Department of Medicinal Chemistry, Uppsala University, BMC P.O. Box 574, SE-751 23, Uppsala, Sweden.
Eur J Pharm Biopharm. 2021 Dec;169:156-167. doi: 10.1016/j.ejpb.2021.10.008. Epub 2021 Oct 20.
The gastrointestinal mucus is a hydrogel that lines the luminal side of the gastrointestinal epithelium, offering barrier protection from pathogens and lubrication of the intraluminal contents. These barrier properties likewise affect nutrients and drugs that need to penetrate the mucus to reach the epithelium prior to absorption. In order to assess the potential impact of the mucus on drug absorption, we need information about the nature of the gastrointestinal mucus. Today, most of the relevant available literature is mainly derived from rodent studies. In this work, we used a larger animal species, the pig model, to characterize the mucus throughout the length of the gastrointestinal tract. This is the first report of the physiological properties (physical appearance, pH and water content), composition (protein, lipid and metabolite content) and structural profiling (rheology and gel network) of the porcine gastrointestinal mucus. These findings allow for direct comparisons between the characteristics of mucus from various segments and can be further utilized to improve our understanding of the role of the mucus on region dependent drug absorption. Additionally, the present work is expected to contribute to the assessment of the porcine model as a preclinical species in the drug development process.
胃肠道黏液是一种水凝胶,排列在胃肠道上皮的腔侧,为病原体提供屏障保护,并对腔内内容物起到润滑作用。这些屏障特性同样会影响需要穿透黏液才能被吸收之前到达上皮的营养物质和药物。为了评估黏液对药物吸收的潜在影响,我们需要了解胃肠道黏液的性质。目前,大部分相关的可用文献主要来源于啮齿动物研究。在这项工作中,我们使用了一个更大的动物物种,即猪模型,来描述整个胃肠道的黏液。这是首次报道猪胃肠道黏液的生理特性(外观、pH 值和含水量)、组成(蛋白质、脂质和代谢物含量)和结构分析(流变学和凝胶网络)。这些发现允许对来自不同部位的黏液特性进行直接比较,并可进一步用于加深我们对黏液在区域依赖性药物吸收中的作用的理解。此外,本工作有望促进将猪模型作为药物开发过程中的临床前物种进行评估。