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用于治疗妊娠相关疾病的纳米颗粒的胎儿风险评估的动态胎盘芯片模型。

Dynamic placenta-on-a-chip model for fetal risk assessment of nanoparticles intended to treat pregnancy-associated diseases.

机构信息

College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166131. doi: 10.1016/j.bbadis.2021.166131. Epub 2021 Mar 22.

Abstract

Pregnant women often have to take medication either for pregnancy-related diseases or for previously existing medical conditions. Current maternal medications pose fetal risks due to off target accumulation in the fetus. Nanoparticles, engineered particles in the nanometer scale, have been used for targeted drug delivery to the site of action without off-target effects. This has opened new avenues for treatment of pregnancy-associated diseases while minimizing risks on the fetus. It is therefore instrumental to study the potential transfer of nanoparticles from the mother to the fetus. Due to limitations of in vivo and ex vivo models, an in vitro model mimicking the in vivo situation is essential. Placenta-on-a-chip provides a microphysiological recapitulation of the human placenta. Here, we reviewed the fetal risks associated with current therapeutic approaches during pregnancy, analyzed the advantages and limitations of current models used for nanoparticle assessment, and highlighted the current need for using dynamic placenta-on-a-chip models for assessing the safety of novel nanoparticle-based therapies during pregnancy.

摘要

孕妇通常需要服用药物来治疗与妊娠相关的疾病或先前存在的医疗状况。目前的孕产妇用药会因药物在胎儿体内非靶向积累而对胎儿造成风险。纳米颗粒是纳米级别的工程颗粒,已被用于靶向药物输送到作用部位,而不会产生非靶向作用。这为治疗妊娠相关疾病开辟了新途径,同时最大限度地降低了对胎儿的风险。因此,研究纳米颗粒从母体向胎儿的潜在转移非常重要。由于体内和体外模型的局限性,模拟体内情况的体外模型是必不可少的。胎盘芯片提供了人类胎盘的微观生理再现。在这里,我们回顾了与妊娠期间当前治疗方法相关的胎儿风险,分析了当前用于评估纳米颗粒的模型的优缺点,并强调了当前需要使用动态胎盘芯片模型来评估新型基于纳米颗粒的治疗方法在妊娠期间的安全性。

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