Abstract：
Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance.
摘要：
肠粘液是一种复杂的天然水凝胶屏障，具有独特的物理性质，阻碍各种口服药物的吸收。从上层水层的冲洗和粘液层的物理阻力都特别影响生物利用度，尤其是,高度水溶性的分子。设计药物制剂的一种潜在策略是添加吸收增强剂(AE)。然而,很少有关于对粘液及其潜在机制起作用的AE的报道，导致不精确的应用。在这项研究中,我们研究了壳寡糖（COS）作为一种安全的，低成本,和有效的口服药物AE。我们揭示了COS与肠粘液层相互作用的流体动力学规律，这与有利于粘液结构重建的吸收有关。基于此,我们设计了一种转化策略,通过在给药前饮用COS溶液来提高一组可溶性口服药物的生物利用度.此外，这项研究有望通过减少药物剂量来扩大其应用范围，例如避免胃肠道刺激和减缓兽用抗生素耐药性。
