生物工程肠表皮的应用用于药物透性和代谢研究
Elisabeth Gill1,2, Stephanie Muenchau Schoepp1,3, Sina Simon2
1Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland. nikolche.gjorevski@roche.com.
Lab on a chip
|November 17, 2025
概括
这项研究引入了一种生物工程肠表皮 (BIE) 模型,用于同时评估口服药物的吸收和代谢. 这种创新系统可以改善药物的生物可用性预测,并有助于药物开发.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物发现 药物发现 药物发现
- 生物技术是生物技术.
背景情况:
- 口服药物管理至关重要,但肠道和肝脏的第一通代谢限制了药物的有效性.
- 目前的体外模型单独评估药物透性和代谢,未能捕捉它们的相互联系.
- 需要改进的体外系统来准确预测人类的药理动力学 (PK) 和口服生物可用性.
研究的目的:
- 描述基于人体有机体的生物工程肠表皮质 (BIE),用于评估药物的透性和代谢.
- 评估BIE的屏障功能,药物代谢酶 (DMEs) 和药物运输体 (DTs).
- 证明BIE在预测药物代谢参数和口服生物可用性的有用性.
主要方法:
- 基于人体器官的生物工程肠表皮质 (BIE) 模型的开发和表征.
- 评估屏障功能,关键药物代谢酶 (DMEs) 和药物载体 (DTs) 的存在.
- 药物运输研究,有针对性的抑制P-糖蛋白 (P-gp) 和乳腺癌抗性蛋白 (BCRP).
- 数学机制建模以预测药物逃离肠道新陈代谢 (Fg) 的部分.
主要成果:
- BIE模型表现出一致的组织模式和验证的屏障功能.
- 关键的药物代谢酶和载体,包括P-gp和BCRP,存在并功能正常.
- BIE系统成功估计了药物代谢参数,预测了逃离肠道代谢 (Fg) 的部分.
结论:
- 生物工程肠表皮 (BIE) 提供了一个新的体外系统,用于同时评估药物的透性和代谢.
- 这种模型对改善口服药物生物可用性预测具有显著的前景.
- 结合in silico建模的BIE系统可以创新药物配方和安全选过程.
相关概念视频
01:16Methods for Studying Drug Absorption: In vitro
562
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...
562
01:27Bioavailability Enhancement: Drug Permeability Enhancement
179
Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
179
01:09Methods for Studying Drug Absorption: In situ
617
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,...
617