Enhanced efficiency of the placental barrier to cisplatin through binding to glycocholic acid

Background and Aims: Cisplatin is a well known cytostatic drug, with high e fficiency against several solid tumours, among which ovarian cancer diagnos ed during pregnancy can be included. The existence of carrier proteins in t he plasma membrane of the trophoblast determines vectorial bile acid transf er across the placenta. Thus, the aim of the present work was to elucidate whether the coupling of cisplatin to a bile acid moiety, such as cholylglyc inate, could endow the resulting drug, Bamet-R2, with enhanced beneficial p roperties; namely, the ability of the placenta to prevent the passage of th e drug toward the foetal compartment. Materials and Methods: On days 15 and 18 of gestation, pregnant rats were anaesthetised with ether and intraveno us administration of 1 mu mol cisplatin or Bamet-R2 was carried out. Follow ing euthanasia on day 21 of pregnancy, samples from the placenta and matern al and foetal kidney, liver, brain, lung, heart, muscle and blood were coll ected and digested to measure tissue drug content by flameless atomic absor ption spectroscopy of platinum. Results: In addition to the beneficial prop erties of Bamet-R2 as regards its much lower toxicity than cisplatin, this study revealed the markedly different abilities of cisplatin and Bamet-R2 t o cross the placenta, which accounts for higher accumulation of cisplatin i n foetal tissues: mainly kidney, lung and heart. Moreover, the amount of dr ug that was found in the placenta itself was several folds higher in animal s treated with cisplatin than in those receiving Bamet-R2. Conclusion: The ability of the placental barrier to more efficiently protect the foetal com partment from cisplatin when the drug was coupled to cholylglycinate sugges ts the potential usefulness of Bamet-R2 as an alternative cytostatic drug i n the treatment of certain tumours during pregnancy.