title: Human placental cell and tissue uptake of doxorubicin and its liposomal formulations.
abstract: The anticancer drug doxorubicin and its liposomal formulations are in clinical use, doxorubicin also during pregnancy. However, little is known about how doxorubicin and its liposomal formulations are taken up by placental cells and whether they can cross human placenta. We therefore investigated quantitative cellular uptake and toxicity of doxorubicin and its two liposomal formulations, pH-sensitive liposomal doxorubicin (L-DOX) and commercially available pegylated liposomal doxorubicin (PL-DOX), in human placental choriocarcinoma (BeWo) cells. PL-DOX showed significantly lower cellular uptake and toxicity compared with doxorubicin and L-DOX. In preliminary studies with human placental perfusion, PL-DOX did not cross the placenta at all in 4h, whereas doxorubicin and L-DOX crossed the placenta at low levels (max 12% of the dose). Furthermore, PL-DOX did not accumulate in placental tissue while doxorubicin did (up to 70% of the dose). Surface pegylation probably explains the low placental cell and tissue uptake of PL-DOX. Formulation of doxorubicin thus seems to enable a decrease of fetal exposure.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address: karoliina.soininen@uef.fi.
authors.forename: Suvi K
authors.initials: SK
authors.lastname: Soininen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Jenni K
authors.initials: JK
authors.lastname: Repo
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Karttunen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Vähäkangas
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Ruponen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008081:Liposomes; D010920:Placenta / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin
keywords: BeWo cells; Doxil; Doxorubicin; Human placental perfusion; Liposome; Pregnancy