Abstract：
Mucus mechanically protects the intestinal epithelium and impacts the absorption of drugs, with a largely unknown role for bile. We explored the impacts of bile on mucosal biomechanics and drug transport within mucus. Bile diffused with square-root-of-time kinetics and interplayed with mucus, leading to transient stiffening captured in Brillouin images and a concentration-dependent change from subdiffusive to Brownian-like diffusion kinetics within the mucus demonstrated by differential dynamic microscopy. Bile-interacting drugs, Fluphenazine and Perphenazine, diffused faster through mucus in the presence of bile, while Metoprolol, a drug with no bile interaction, displayed consistent diffusion. Our findings were corroborated by rat studies, where co-dosing of a bile acid sequestrant substantially reduced the bioavailability of Perphenazine but not Metoprolol. We clustered over 50 drugs based on their interactions with bile and mucin. Drugs that interacted with bile also interacted with mucin but not vice versa. This study detailed the dynamics of mucus biomechanics under bile exposure and linked the ability of a drug to interact with bile to its abbility to interact with mucus.
摘要：
粘液机械地保护肠上皮并影响药物的吸收，胆汁的作用在很大程度上是未知的。我们探讨了胆汁对粘膜生物力学和粘液内药物运输的影响。胆汁以时间平方根动力学扩散，并与粘液相互作用，导致布里渊图像中捕获的瞬时硬化，以及通过差分动态显微镜证明的粘液内从亚扩散到布朗样扩散动力学的浓度依赖性变化。胆汁相互作用药物,氟奋乃静和奋乃静,在胆汁存在的情况下通过粘液扩散得更快，而美托洛尔,一种没有胆汁相互作用的药物，显示一致的扩散。我们的发现得到了大鼠研究的证实,其中胆汁酸螯合剂的共同给药大大降低了奋乃静的生物利用度，而不是美托洛尔。根据它们与胆汁和粘蛋白的相互作用，我们聚集了50多种药物。与胆汁相互作用的药物也与粘蛋白相互作用，但反之亦然。这项研究详细介绍了胆汁暴露下粘液生物力学的动力学，并将药物与胆汁相互作用的能力与其与粘液相互作用的能力联系起来。
