Enhanced Intestinal Absorption of Proteins via a Natural Metabolite-Based Deep Eutectic System.

A natural metabolite-based deep eutectic system composed of betaine and lactic acid (BL-DES) was developed as a food-grade strategy to enhance intestinal absorption of proteins. Insulin was selected as a model protein for convenient and reliable assessment of intestinal absorption. BL-DES reduced the viscosity of simulated intestinal mucus and increased insulin permeability through the mucus layer. Jejunal administration of insulin@BL-DES showed a significant hypoglycemic effect. Hematological, cellular, and histological evaluations confirmed the favorable biocompatibility of BL-DES. Mechanistic investigations revealed that BL-DES promotes paracellular transport through reversible opening of tight junctions.