Formulation effects on paclitaxel transfer and uptake in the human placenta

Area of Science:

• Obstetrics and Gynecology
• Pharmacology and Toxicology
• Oncology

Background:

• Breast cancer during pregnancy poses risks to both mother and fetus.
• New paclitaxel nanoformulations offer improved dosing and side effect profiles for cancer treatment.
• Transplacental transport and fetal exposure to these nanoformulations are not well understood.

Purpose of the Study:

• To investigate the transplacental transport of three paclitaxel nanoformulations: Taxol, Abraxane, and Genexol-PM.
• To determine fetal exposure levels and maternal pharmacokinetics associated with each formulation.
• To assess the impact of nanoformulation properties on placental drug accumulation and efflux.

Main Methods:

• Utilized an ex vivo dually perfused human placental cotyledon model.
• Conducted in vitro studies with nanoformulations and fluorescent nanoparticle analogs.
• Measured paclitaxel concentrations in maternal and fetal compartments over time.
• Investigated the interaction of nanoformulations with P-glycoprotein efflux pumps.

Main Results:

• Genexol-PM exhibited higher placental accumulation compared to Taxol.
• Both Genexol-PM and Abraxane resulted in lower maternal paclitaxel concentrations over time compared to Taxol.
• Genexol-PM demonstrated the ability to bypass P-glycoprotein efflux, unlike Abraxane, which behaved as a free drug.

Conclusions:

• Paclitaxel nanoformulations differ significantly in their placental transport and fetal exposure potential.
• Genexol-PM's ability to overcome efflux mechanisms warrants further investigation for safety in pregnancy.
• Findings will inform the development of safer breast cancer treatment strategies for pregnant patients.