Targeted lipid nanoparticles to prevent trans-placental passage in the ex vivo human placental cotyledon perfusion model

Abstract Background: Medication use during pregnancy poses risks to both the mother and the fetus. These risks include an elevated potential for fetotoxicity due to placental drug transport. Nanomedicines offer a promising solution by potentially preventing trans-placental passage. Targeted nanomedicines could enhance safety and efficacy in treating maternal or placental pathophysiology. Our study investigates placental transfer kinetics of targeted lipid nanoparticles (LNPs) in an ex vivo human placenta cotyledon perfusion model. Methods: We collected human placentas for dual-side ex vivo placental perfusions. Targeted lipid LNPs with a fluorescence tag were introduced into the maternal circuit of each placenta. To establish if there was trans-placental passage of LNPs to the fetal circuit, we collected samples from maternal and fetal circuits throughout the six hours of the perfusion. We determined the fluorescence signal using a multi-mode microplate reader and Multiphoton microscopy to localize the the LNPs in the placenta tissue. Results: Data from perfused placenta tissue showed no significant transfer of the fluorescently labeled LNPs across the placental barrier to the fetal circuit. Localization of targeted LNP in tissue samples is mainly observed in the maternal blood space of the placenta. Conclusion: Our results suggest that targeted LNPs present a promising strategic approach to prevent trans-placental passage to the fetus. Our future perspectives involve investigating the efficacy of targeted LNPs as well as loading targeted LNPs with nucleic acid-based therapeutics to investigate their therapeutic potential.