Human Primary Cell-Based Organotypic Microtissues for Modeling Small Intestinal Drug Absorption.
Human Primary Cell-Based Organotypic Microtissues for Modeling Small Intestinal Drug Absorption.
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DOI：
10.1007/s11095-018-2362-0
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发表时间：
2018-02-23
影响因子：
3.7
通讯作者：
Klausner M
中科院分区：
文献类型：
--
作者：
Ayehunie S;Landry T;Stevens Z;Armento A;Hayden P;Klausner M
该研究评估了新的体外原发性人细胞基有机小肠（SMI）微作用的使用，以预测肠道药物滥用和药物毒用的相互作用。
使用人肠成纤维细胞和在可渗透的支持下培养的肠肠细胞对SMI微动物进行了重建，以评估肠道微动物的适用性，以模拟药物滥用，并确定微动物的渗透率系数CACO-2渗透性数据使用外排蛋白底物和抑制剂检查。
3D - 智能微动物概括了人类小肠的结构特征和物理屏障特性。与CACO-2细胞相比，与人类受苦数据（R2 = 0.91）相关（R2 = 0.71）使用外排底物和抑制剂证实了外排转运蛋白的功能，从而导致> 2.0倍的外排比，并在添加抑制剂后通过降低外排比。
SMI微作用似乎是预测口服药物的药物生物利用度的有用临床前工具。
The study evaluates the use of new in vitro primary human cell-based organotypic small intestinal (SMI) microtissues for predicting intestinal drug absorption and drug-drug interaction. The SMI microtissues were reconstructed using human intestinal fibroblasts and enterocytes cultured on a permeable support. To evaluate the suitability of the intestinal microtissues to model drug absorption, the permeability coefficients across the microtissues were determined for a panel of 11 benchmark drugs with known human absorption and Caco-2 permeability data. Drug-drug interactions were examined using efflux transporter substrates and inhibitors. The 3D–intestinal microtissues recapitulate the structural features and physiological barrier properties of the human small intestine. The microtissues also expressed drug transporters and metabolizing enzymes found on the intestinal wall. Functionally, the SMI microtissues were able to discriminate between low and high permeability drugs and correlated better with human absorption data (r2 = 0.91) compared to Caco-2 cells (r2 = 0.71). Finally, the functionality of efflux transporters was confirmed using efflux substrates and inhibitors which resulted in efflux ratios of >2.0 fold and by a decrease in efflux ratios following the addition of inhibitors. The SMI microtissues appear to be a useful preclinical tool for predicting drug bioavailability of orally administered drugs.
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DOI：
10.1016/j.ejpb.2015.03.002
发表时间：
2015-09
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
--
作者：
Maschmeyer I;Hasenberg T;Jaenicke A;Lindner M;Lorenz AK;Zech J;Garbe LA;Sonntag F;Hayden P;Ayehunie S;Lauster R;Marx U;Materne EM
通讯作者：
Materne EM
DOI：
10.1002/adma.201603270
发表时间：
2016-11
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Anselmo AC;McHugh KJ;Webster J;Langer R;Jaklenec A
通讯作者：
Jaklenec A
影响因子：
12.2
作者：
Maldonado-Contreras, Ana;Birtley, James R.;McCormick, Beth A.
通讯作者：
McCormick, Beth A.
使用蛋白质工程底物改善CACO-2药物筛选模型中细胞细胞运输的改善。
影响因子：
14
作者：
DiMarco RL;Hunt DR;Dewi RE;Heilshorn SC
通讯作者：
Heilshorn SC
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM