与Caco-2单培养相比，Caco-2 / HT29-MTX和Caco-2 / HT29-MTX / Raji B共培养模型对预测肠和结肠通透性的有用性,Molecular Pharmaceutics

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与Caco-2单培养相比，Caco-2 / HT29-MTX和Caco-2 / HT29-MTX / Raji B共培养模型对预测肠和结肠通透性的有用性
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-03-10 00:00:00 , DOI: 10.1021/acs.molpharmaceut.6b01165
Isabel Lozoya-Agullo _{1,

2} , Francisca Araújo _{3,

4} , Isabel González-Álvarez ₁ , Matilde Merino-Sanjuán _{2,

5} , Marta González-Álvarez ₁ , Marival Bermejo ₁ , Bruno Sarmento _{3,

4,

6}

Affiliation

Caco-2细胞单层是体外被广泛接受的该模型可预测人类的通透性，但存在一些关键性的局限性。因此，已开发出一些尽可能接近人类肠上皮的替代细胞培养物，以实现更多的生理条件，例如Caco-2 / HT29-MTX共培养和三重Caco-2 / HT29-MTX / RajiB。楷模。在这项工作中，评估了共培养和三重共培养模型中不同生物制药分类系统（BCS）特性的12种模型药物的渗透性。另外，还仔细研究了两种模型根据BCS标准对化合物进行分类的实用性。获得的结果表明，Caco-2 / HT29-MTX的共培养和Caco-2 / HT29-MTX / Raji B的三重共培养是预测肠道通透性和根据BCS将药物分类为高通透性或低通透性的有用模型。。此外，要彻底研究特定药物的转运机制，使用比Caco-2单培养更为复杂的模型更为合适，因为共培养和三重共培养是更生理的模型，因此，用它们获得的结果将更接近于通过Caco-2单培养获得的结果。人的肠子。

"点击查看英文标题和摘要"

Usefulness of Caco-2/HT29-MTX and Caco-2/HT29-MTX/Raji B Coculture Models To Predict Intestinal and Colonic Permeability Compared to Caco-2 Monoculture

The Caco-2 cellular monolayer is a widely accepted in vitro model to predict human permeability but suffering from several and critical limitations. Therefore, some alternative cell cultures to mimic the human intestinal epithelium, as closely as possible, have been developed to achieve more physiological conditions, as the Caco-2/HT29-MTX coculture and the triple Caco-2/HT29-MTX/Raji B models. In this work the permeability of 12 model drugs of different Biopharmaceutical Classification System (BCS) characteristics, in the coculture and triple coculture models was assessed. Additionally, the utility of both models to classify compounds according to the BCS criteria was scrutinized. The obtained results suggested that the coculture of Caco-2/HT29-MTX and the triple coculture of Caco-2/HT29-MTX/Raji B were useful models to predict intestinal permeability and to classify the drugs in high or low permeability according to BCS. Moreover, to study thoroughly the transport mechanism of a specific drug, using a more complex model than Caco-2 monocultures is more suitable because coculture and triple coculture are more physiological models, so the results obtained with them will be closer to those obtained in the human intestine.

更新日期：2017-03-10

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