van Kammen Caren, van Hove Hedwig, Kapsokalyvas Dimitrios, Greupink Rick, Schiffelers Raymond, Lely Titia, Terstappen Fieke
Department of Nanomedicine, LAB CDL Research, UMC Utrecht, Utrecht, The Netherlands.
Department of Pharmacy, Division of Pharmacology and Toxicology, Radboud UMC, Nijmegen, The Netherlands.
Drug Deliv Transl Res. 2025 Jun;15(6):1985-1993. doi: 10.1007/s13346-024-01715-6. Epub 2024 Oct 14.
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. We collected human placentas for dual-side ex vivo placental perfusions. Targeted 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 LNPs in the placenta tissue. 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 LNPs in tissue samples is mainly observed in the maternal blood space of the placenta. 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.
孕期用药对母亲和胎儿均有风险。这些风险包括由于胎盘药物转运导致的胎儿毒性增加的可能性。纳米药物通过潜在地阻止跨胎盘转运提供了一个有前景的解决方案。靶向纳米药物可以提高治疗母体或胎盘病理生理学的安全性和有效性。我们的研究在体外人胎盘小叶灌注模型中研究了靶向脂质纳米颗粒（LNP）的胎盘转移动力学。我们收集人胎盘用于双侧体外胎盘灌注。将带有荧光标签的靶向LNP引入每个胎盘的母体循环中。为了确定LNP是否通过胎盘进入胎儿循环，我们在灌注的六个小时内从母体和胎儿循环中采集样本。我们使用多模式微孔板读数器和多光子显微镜确定荧光信号，以在胎盘组织中定位LNP。来自灌注胎盘组织的数据显示，荧光标记的LNP没有明显穿过胎盘屏障进入胎儿循环。在组织样本中，靶向LNP的定位主要在胎盘的母体血腔中观察到。我们的结果表明，靶向LNP是一种有前景的策略性方法，可以防止药物通过胎盘进入胎儿体内。我们未来的展望包括研究靶向LNP的疗效，以及用基于核酸的治疗剂装载靶向LNP，以研究它们的治疗潜力。
