Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs.

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. Schematic illustration of COS pro-absorptive action mechanisms and its rational use. Firstly, the oral COS solution interacts with the intestinal mucus. Over time, COS can reconstruct the physical properties of the mucus layer. In addition, COS's intrinsic amino cation interacts electrostatically with MUC-2, changing the local viscosity of the mucus. This mode creates a favorable environment for hydrophilic drug molecules to pass through the mucus barrier when oral high water-soluble drugs can be better absorbed and oral bioavailability is improved. [Display omitted] • Chitooligosaccharide (COS) can reconstitute the drug absorption relevant intestinal mucus structure, including thickness, pore space, viscosity, etc. • The hydrodynamic model reveals the pro-absorption mechanism of COS and simulates the process of drug absorption. • This pro-absorption strategy can especially enhance the oral absorption of water-soluble drugs, potentially reduce toxicity and increase efficacy. [ABSTRACT FROM AUTHOR]