Assessing Drug Transport Across the Human Placental Barrier: From In Vivo and In Vitro Measurements to the Ex Vivo Perfusion Method and In silico Techniques

Constantinos      Giaginis; Anna      Tsantili-Kakoulidou; Stamatios      Theocharis

Abstract

Assessing drug transport across the human placental barrier is of vital importance in order to guarantee drug safety during pregnancy. However, due to ethical reasons, in vivo fetal development risk assessment studies related to maternal drugs and chemicals exposure remain extremely limited. To overcome any ethical issues, several in vitro models applying primary trophoblastic cells, immortal cell lines and tissue explants of placental origin have recently been advanced. Alternatively, ex vivo human placental perfusion seems to be a more representative and highly informative method, which offers better insights into the different drug transporters, xenobiotic metabolism and tissue binding. Recently, in silico techniques have further been advanced as complementary tools to validate experimental placental transfer data, offering an attractive alternative for high throughput screening of potential fetotoxicity at the early stages of drug design. The present review scrutinizes, from a critical point of view, the current trends and perspectives in the emerging topic of drug transport across the human placental barrier. The special characteristics of the recently developed biopharmaceuticals on the transplacental transfer process are also discussed.

Keywords: Biopharmaceuticals, ex vivo placental perfusion, in silico modeling, physicochemical properties, placental transfer, risk assessment, drug safety during pregnancy, xenobiotic metabolism, fetotoxicity, intrauterine growth retardation, growth restriction (IUGR)