Transport and metabolism of opioid peptides across BeWo cells, an in vitro model of the placental barrier

Abstract

. (2002) Transport and metabolism of opioid peptides across BeWo Cells, an in vitro model of the placental barrier. Int. J. Pharm. 233,[85][86][87][88][89][90][91][92][93][94][95][96][97][98] 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.

Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model

“…The BeWo b30 human placental choriocarcinoma cell line is considered an established model of the human placental barrier (Ampasavate et al, 2002). When the cells are grown on permeable inserts, they form polarized monolayers useful for studying transplacental transport (Bode et al, 2006).…”

Transport and biodistribution of dendrimers across human fetal membranes: Implications for intravaginal administration of dendrimer-drug conjugates

“…Previously, an inverse relation with the molecular weight and the transport across the BeWo (choriocarcinoma) cell line was observed for various markers such as fluorescein, sucrose, dextans and several amino acids of varying molecular weights[44, 45]. The molecular sieving of the BeWo monolayers seemed to restrict the transport of peptides > 1033 Da and the paracellular route was major pathway for transport [45]. Our results for the G 4 -PAMAM dendrimer ( 1 ) seem to be in agreement with those reported.…”

The Role of the Placenta in Fetal Exposure to Xenobiotics: Importance of Membrane Transporters and Human Models for Transfer Studies

“…These advantages make this cell line an attractive in vitro model for studying trans-trophoblast transport and drug metabolism (Poulsen et al, 2009), as shown by numerous studies on the transport of digoxin, vinblastine, vincristine (Ushigome et al, 2000), opioides peptides (Ampasavate et al, 2002), iron (Heaton et al, 2008), and cholesterol (Schmid et al, 2003) (Table 4).…”