Effects of hydrophobicity and molecular weight on the transport permeability of oligopeptides across Caco‐2 cell monolayers

The objective of this paper was to investigate the effects of hydrophobicity and molecular weight (MW) on the transepithelial transport permeability of oligopeptides across Caco-2 cell monolayers. Results showed that oligopeptides with different N-terminal amino acids had a wide range of permeability values and could be divided into three levels according to their correlations with log D and MW. At a good level of permeability, the permeability was positively correlated with log D, but negatively correlated with MW (p < .001); at an intermediate level of permeability, the permeability was negatively correlated with log D and MW (p < .001); and at a low level of permeability, the permeability was positively correlated with log D and MW (p < .01). These results suggest for the first time that the transport of oligopeptides across Caco-2 cell monolayers might be closely related to their molecular properties of log D and MW. PRACTICAL APPLICATIONS: A great number of food-derived bioactive peptides display health-promoting effects and show potential as bioactive ingredients in functional foods. However, the poor absorption in the intestine limits the application of food bioactive peptides, especially for the oligopeptides containing more than three amino acids. Although the transepithelial transport of food-derived oligopeptides in the intestinal epithelium has been widely reported, its transport mechanism is still obscure. Our study shows a three-level relationship between the transport permeability and log D and MW of oligopeptides across Caco-2 cell monolayers and provides a novel evidence for the coexistence of transcellular and paracellular pathways for the transport of oligopeptides through the intestine. This result will contribute to the understanding of the transport mechanisms of oligopeptides in the intestine.