Bioavailability of antihypertensive lactoferricin B-derived peptides: Transepithelial transport and resistance to intestinal and plasma peptidases

Abstract

The transepithelial transport of the angiotensin I-converting enzyme (ACE)-inhibitory and antihypertensive lactoferricin B (LfcinB)-derived hexapeptide LfcinB20–25 (RRWQWR) and of its two main fragments RWQ and WQ were investigated using a human intestinal cell (Caco-2) monolayer. The three peptides were susceptible to the action of brush-border peptidases. Intact LfcinB20–25 was not transported across Caco-2 whereas RWQ and WQ were both absorbed through the cell monolayer. Apparent permeability (Papp) values for absorptive transport across the monolayer were 0.7 × 10−8 cm s−1 (RWQ) and 3.9 × 10−8 cm s−1 (WQ). The effect of pathway-selective inhibitors on peptide absorption suggested paracellular diffusion as the main mechanism for the transport of intact RWQ and WQ. In vitro incubation in human plasma showed half-life values of 1.9 min (RWQ) and 2.3 h (WQ). These results highlight the possibility of transport of antihypertensive lactoferricin B-derived peptides across human intestinal mucosa.