Human respiratory epithelial cell culture for drug delivery applications
Human respiratory epithelial cell culture for drug delivery applications
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DOI：
10.1016/j.ejpb.2005.02.010
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发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Ehrhardt, C
中科院分区：
文献类型：
--
作者：
Forbes, B;Ehrhardt, C
在向肺输送药物方面的最新进展推动了对体外方法的需求，以评估吸入药物的命运。动物实验的限制促进了使用人呼吸道上皮细胞培养物来模拟肺的吸收屏障：两种气道细胞系，16HBE14o-和Calu-3，以及原代培养的人肺泡i型样细胞（hAEpC）得到了重视。这些体外模型的渗透性与报道的原生肺上皮相当。这与A549人肺泡细胞系的高通透性形成对比，不适合用于药物通透性实验。在“吸收”和“分泌”方向测量的化合物的表观渗透性系数（P-app）表显示，与Calu-3细胞（bbb50）相比，16HBE14o-细胞和hAEpC中评估的化合物（< 15）较少。化合物的载体（不对称）转运在三种细胞类型中被报道，p糖蛋白是研究最多的转运机制，在所有的报道中。在肺吸收的体内外相关性和使用培养的呼吸细胞评估药物代谢、毒性和靶向策略方面正在取得进展。总之，人类呼吸道上皮细胞层的培养方法已经建立，关于其渗透性特征和肺模型适用性的数据正在变得可用。辨别在哪些情况下使用人类呼吸细胞模型将是必要的，或者提供优于非器官，非物种特异性细胞模型的优势。是下一个挑战。(c) 2005 Elsevier B.V.版权所有
Recent developments in delivering drugs to the lung are driving the need for in vitro methods to evaluate the fate of inhaled medicines. Constraints on experimentation using animals have promoted the use of human respiratory epithelial cell cultures to model the absorption barrier of the lung: with two airway cell lines, 16HBE14o- and Calu-3, and primary cultured human alveolar type I-like cells (hAEpC) gaining prominence. These in vitro models develop permeability properties which are comparable to those reported for native lung epithelia. This is in contrast to the high permeability of the A549 human alveolar cell line, which is unsuitable for use in drug permeability experiments. Tabulation of apparent permeability coefficients (P-app) of compounds measured in 'absorptive' and 'secretory' directions reveals that fewer compounds (< 15) have been evaluated in 16HBE14o- cells and hAEpC compared to Calu-3 cells (> 50). Vectorial (asymmetric) transport of compounds is reported in the three cell types with P-glycoprotein, the most studied transport mechanism, being reported in all. Progress is being made towards in vitro-in vivo-correlation for pulmonary absorption and in the use Of Cultured respiratory cells to evaluate drug metabolism, toxicity and targeting strategies. In summary, methods for the culture of human respiratory epithelial cell layers have been established and data regarding their permeability characteristics and suitability to model the lung is becoming available. Discerning the circumstances under which the use of human respiratory cell models will be essential, or offers advantages over non-organ, non-species specific cell models. is the next challenge. (c) 2005 Elsevier B.V. All rights reserved.