Transport and Metabolism of Opioid Peptides across BeWo Cells, An In Vitro Model of the Placental Barrier

Abstract

In keeping with the advance of biotechnology, cell culture becomes an important tool for investigating the transport and the metabolism phenomena. A cell line of human origin, the BeWo choriocarcinoma cell line, was used for the study of the transport and metabolism of opioid peptides across the in vitro model of the placental barrier. Opioid peptides, both naturally occurring and their synthetic analogs, are of interest to be developed as potent analgesics and were included in this study. The apparent permeability coefficients of the peptides containing 4 to 11 amino acid or analog residues were in the range of 0.23-14.60 x 10-5 cm/sec. The apparent permeability coefficients of these peptides were comparable to those of sucrose or dextrans, hydrophilic markers. Molecular weight and size of the peptides were inversely correlated to the permeability across the BeWo monolayers. Lipophilicity and charges of the peptides were also investigated and found to be the minor factors regulating the extent of peptide permeation. Contrasting to the transport of DPDPE peptide analog across the blood-brain barrier, the transport of DPDPE across the BeWo monolayers were not found to be via carrier-mediated transport. The major transport pathway of the opioid peptides across the BeWo monolayers was found to be via paracellular route. In metabolism studies, aminopeptidase was found to be a major enzyme type responsible for the degradation of naturally occurring peptides but not for the synthetic analogues. The finding obtained from the present study reveal the applicability of the BeWo cell line to be used as the in vitro cell culture model for the transport and metabolism screening of the opioid peptides.