Structural Requirement of Casein Peptides for Transcytosis through the Caco-2 Cell Monolayer: Hydrophobicity and Charge Property Affect the Transport Pathway and Efficiency.

Casein is a rich source of bioactive peptides with complete amino acid composition. In this study, the casein peptides identified in our previous study with different hydrophobicities and charge properties were employed to investigate the transport efficiency via the transcytosis pathway across Caco-2 cell monolayers. Results revealed that the apparent permeability coefficient (Papp) values of transcytosis exhibited a linear correlation with a pI of positively charged peptides during bidirectional transport. A similar law was found as for the peptides with different hydrophobicities. The transcytosis route of Pep-II to Pep-VII appears to be the clathrin- and caveolin-independent transcytosis pathway as well as caveolae-mediated transcytosis pathway, showing a linear correlation with Papp values, respectively. Additionally, no direct correlation was shown between the hydrophobicity of peptides and clathrin-mediated transcytosis. Our results help to increase the bioaccessibility of peptide drugs across intestinal mucosa by developing strategies to alter the physicochemical properties without changing bioactivity.