Peptide transport and metabolism across the placenta

Advances made in the field of DNA and recombinant technology have led to the emergence of peptides and proteins as an important class of therapeutic compounds. While a significant amount of information exists regarding the transport and metabolism of peptides across different barriers (e.g. gastro-intestinal, nasal, and blood-brain barrier), Limited attention has been paid towards their transport and metabolism across the placental barrier. The mechanism of placental transport of peptides is of importance in assessing the exposure of these drugs to the fetus, particularly when the drugs potentially may have adverse effects on the developing fetus. The absence of a well accepted, simple and convenient animal model may be a reason for the limited information available on the placental transport and metabolism of peptides. Although several in vivo models have been utilized to study the transport and metabolism of drugs across the placenta, species differences in the placental physiology and anatomy of the animal models with regard to the human placenta have prevented their widespread use. The in vitro human placental cell culture models are morphologically similar to the trophoblasts and often express the enzymes and carrier systems found in the human placenta. They can provide an easy and rapid method to determine the mechanisms of transport and metabolism of drugs across the placental barrier. These in vitro models have been utilized in the determination of transport mechanisms of drugs of abuse across the placenta. This article overviews the available literature on the placental transport of peptides and describes the application of an in vitro cell culture model (BeWo) to determine the mechanisms of transport of opioid peptides and their analogues across the placenta. (C) 1999 Elsevier Science B.V. All rights reserved.