Paclitaxel nanoparticles for breast cancer therapy in pregnancy
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Breast cancer can complicate pregnancy and result in fetal and maternal morbidity and mortality. These effects are often compounded by restrictions in the diagnosis and treatment of breast cancer due to implications on fetal health. A number of new paclitaxel nanoformulations for the treatment of breast cancer are entering clinical studies or are commercially available, but whether or not these formulations cause differences in transplacental transfer and, ultimately, fetal exposure remains to be seen. Here, we examined three formulations of paclitaxel—Taxol, or paclitaxel dissolved in Cremophor-EL; Abraxane, an albumin nanoparticle; and Genexol-PM, a polymeric micelle. Using the ex vivo dually perfused human placental cotyledon, we were able to show that paclitaxel transfer appears to be similar across the formulations, but the maternal concentrations and placental accumulation varies significantly. This is likely due to the interaction of the materials with the placental trophoblast, so we also examined the formulations in a trophoblast cell model for their susceptibility to efflux, as well as the permeability and uptake of fluorescent nanoparticle analogues. We found that Genexol-PM allows paclitaxel to overcome P-gp efflux and crosses the trophoblast to a significant extent, while Abraxane behaves like a free drug formulation. Cremophor-EL in Taxol is believed to cause differences in paclitaxel permeability across the apical trophoblast membrane as well. We anticipate that these findings will have an impact on the future design of pharmaceuticals tailored to pregnancy-related diseases, but also in the development of rational and safe treatment strategies for pregnancy-associated breast cancer and other diseases.