对微生理学人类胎盘屏障模型的评估,用于研究胎盘药物转移
Shekh Rahman1, Brian Kwee2, Miao Li3
1Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States; Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
Reproductive toxicology (Elmsford, N.Y.)
|December 13, 2023
概括
微生理系统 (MPS) 为研究胎盘药物转移和预测胎儿暴露提供了更准确的模型. 这项研究证明了MPSs.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 生物医学工程 生物医学工程
背景情况:
- 评估胎儿药物毒性和出生缺陷风险需要了解胎盘药物运输.
- 现有的体内和体外模型在准确评估胎盘药物转移和毒性方面存在局限性.
- 微生理系统 (MPS) 为药物开发和毒理学提供先进的微型生理模型.
研究的目的:
- 开发和验证人类胎盘屏障的微生理系统 (MPS) 模型.
- 用开发的MPS来研究胎盘药物转移,并将其与跨井模型进行比较.
- 评估MPS在预测胎儿药物暴露和药理动力学特征方面的潜力.
主要方法:
- 使用人类胎盘上皮和内皮细胞构建了多层水凝膜式MPS.
- 通过评估单层形成,细胞间连接,透性和结构完整性来表征胎盘屏障模型.
- 研究了三个小分子药物的胎盘转移 (glyburide,rifaximin,咖啡因) 并根据体外数据估计了人类的药理动力学.
主要成果:
- 三种研究药物 (甘胺,利法西明,咖啡因) 都成功穿越了胎盘屏障模型.
- 药物转移率与分子量相反相关:甘化物 (494Da) <利法西明 (785.9Da) <咖啡因 (194.19Da).
- 非分区分析使得从MPS和transwell模型数据中估计人类的药理动力学特征.
结论:
- 开发的MPS有效地复制了人类胎盘屏障的关键结构和功能.
- MPS显示出作为一种有价值的体外工具的潜力,用于研究胎盘药物转移和预测胎儿药物暴露.
- 使用MPS的进一步研究可以为怀孕期间的药物药理动力学提供关键的见解.
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