PMID- 26383631 OWN - NLM STAT- MEDLINE DCOM- 20160125 LR - 20151010 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 239 IP - 2 DP - 2015 Dec 3 TI - Human placental cell and tissue uptake of doxorubicin and its liposomal formulations. PG - 108-14 LID - S0378-4274(15)30051-5 [pii] LID - 10.1016/j.toxlet.2015.09.011 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Soininen, Suvi K AU - Soininen SK AD - 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. FAU - Repo, Jenni K AU - Repo JK AD - School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. FAU - Karttunen, Vesa AU - Karttunen V AD - School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. FAU - Auriola, Seppo AU - Auriola S AD - School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. FAU - Vahakangas, Kirsi H AU - Vahakangas KH AD - School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. FAU - Ruponen, Marika AU - Ruponen M AD - School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, FI-70211 Kuopio, Finland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150914 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Liposomes) RN - 80168379AG (Doxorubicin) SB - IM MH - Antibiotics, Antineoplastic/administration & dosage/*pharmacokinetics MH - Cell Line, Tumor MH - Cell Survival MH - Doxorubicin/administration & dosage/analogs & derivatives/chemistry/*pharmacokinetics MH - Female MH - Humans MH - Liposomes MH - Placenta/*cytology/*metabolism MH - Pregnancy OTO - NOTNLM OT - BeWo cells OT - Doxil OT - Doxorubicin OT - Human placental perfusion OT - Liposome OT - Pregnancy EDAT- 2015/09/19 06:00 MHDA- 2016/01/26 06:00 CRDT- 2015/09/19 06:00 PHST- 2015/07/09 00:00 [received] PHST- 2015/09/08 00:00 [revised] PHST- 2015/09/11 00:00 [accepted] PHST- 2015/09/19 06:00 [entrez] PHST- 2015/09/19 06:00 [pubmed] PHST- 2016/01/26 06:00 [medline] AID - S0378-4274(15)30051-5 [pii] AID - 10.1016/j.toxlet.2015.09.011 [doi] PST - ppublish SO - Toxicol Lett. 2015 Dec 3;239(2):108-14. doi: 10.1016/j.toxlet.2015.09.011. Epub 2015 Sep 14.