人体器官型结肠体外微组织:揭开了结肠药物处置的新窗口
Pedro G M Canhão1, Jan Snoeys2, Suzy Geerinckx2
1Preclinical Sciences & Translational Safety, Johnson & Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium; Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - box 921, 3000 Leuven, Belgium.
概括
作为3D结肠微组织的EpiColon有效地模拟了结肠的药物处置和透性,显示出作为Caco-2单层替代品的前景. 它准确地预测药物吸收,并反映人类结肠组织特征.
科学领域:
- 药理学和药物开发领域
- 生物技术和组织工程
- 胃肠病学研究 胃肠病学研究
背景情况:
- 目前的体外模型,如Caco-2单层,在完全回顾人类结肠药物处置方面存在局限性.
- 需要先进的模型来更好地预测体内药物行为.
- 有机型的3D微组织为药物透性研究提供了一个更具生理相关性的平台.
研究的目的:
- 为了评估EpiColon,一个新型的人类器官型的3D结肠微组织,以评估结肠药物处置的能力.
- 在药物透性排名中,比较EpiColon与传统Caco-2单层的性能.
- 为了描述EpiColon的屏障功能,形态和传送器活动.
主要方法:
- 埃皮科隆微组织的特征是屏障功能 (TEER),形态 (组织学,IHC) 和药物运输 (P).
- 使用FITC-dextran和[14C]mannitol来确定完整性的值.
- 使用20种基准药物来比较EpiColon和Caco-2之间的透性;评估了流体输送活性 (MDR1/P-gp,MRP2,BCRP).
主要成果:
- 埃皮科隆证明了生理障碍功能,并有效地区分高和低透性的化合物.
- 与Caco-2相比,该模型显示了功能性流出输送器活性和在低透度下增强的动态范围.
- 在EpiColon的Papp和被吸收的人类分数 (fabs) 之间发现了显著的相关性,类似于Caco-2.
结论:
- EpiColon是一种有前途的3D结肠微组织模型,用于评估结肠药物处置和透性.
- 它作为Caco-2单层的宝贵补充,提供了更好的生理相关性和预测能力.
- 需要进一步优化以解决细胞形态和吞吐量,以便在研究和工业中更广泛地适用.
相关概念视频
01:16Methods for Studying Drug Absorption: In vitro
199
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
199
01:09Methods for Studying Drug Absorption: In situ
201
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
201