Human placental cell and tissue uptake of doxorubicin and its liposomal formulations

• Published in: Toxicology letters 2015-12, Vol.239 (2), p.108-114
• Main Authors: Soininen, Suvi K., Repo, Jenni K., Karttunen, Vesa, Auriola, Seppo, Vähäkangas, Kirsi H., Ruponen, Marika
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; BeWo cells; Cell Line, Tumor; Cell Survival; Cellular; Doxil; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Female; Formulations; Human; Human placental perfusion; Humans; Liposome; Liposomes; Low level; Placenta; Placenta - cytology; Placenta - metabolism; Pregnancy; Toxicity; Uptakes
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2015.09.011

•Human placental cell and tissue uptake of doxorubicin was significant.•Doxorubicin crossed placenta at low levels within 4-h human placental perfusion.•Pegylated liposomal doxorubicin was weakly taken up by human placental cells.•Pegylated liposomal doxorubicin did not cross human placenta in 4-h perfusion. 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.