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首页> 外文期刊>European journal of drug metabolism and pharmacokinetics >Is RPMI 2650 a Suitable In Vitro Nasal Model for Drug Transport Studies?
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Is RPMI 2650 a Suitable In Vitro Nasal Model for Drug Transport Studies?

机译：RPMI 2650是一种适用于药物运输研究的体外鼻模式吗？

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摘要

The evaluation of new intranasal medications requires the development of in vitro cell model suitable for high-throughput screening studies. The aim of a pharmacological model is to closely mimic the barrier properties of human nasal mucosa that will influence drug pharmacokinetics. In this context, the human nasal cell line RPMI 2650 has been investigated over these last years. Although the initial studies tended to demonstrate strong physiological correlations between RPMI 2650 cells and nasal mucosa, the variability of experimental designs does not allow a clear comparison of actual data. Thereby, the standardization of cell culture parameters is crucial to obtain a stronger reproducibility and increase the relevance of data. Indeed, RPMI 2650 barrier properties are heavily dependent of cell culture conditions, especially of the physiological air-liquid interface that strengthen the expression of both tight junction proteins and drug transporters. Conversely, cell culture medium and insert composition showed a minor impact on the four key parameters of a nasal barrier. Despite the recent advances in the physiological characterization of RPMI 2650 model, only limited pharmacological data are available concerning the involvement of drug transporters in drug bioavailability. The deployment of standardized bi-directional permeability studies using reference compounds is required to determine the relevance of RPMI 2650 model in the field of drug transport studies.
机译：新的鼻内药物的评价需要适合于高通量筛选研究的体外细胞模型的发展。药理学模型的目的是密切模仿人鼻腔粘膜的阻隔性，这将影响药物药代动力学。在这种情况下，在过去几年中已经研究了人鼻细胞系RPMI 2650。虽然初步研究趋于证明RPMI 2650细胞和鼻粘膜之间的强烈生理相关性，但实验设计的可变性不允许明确比较实际数据。由此，细胞培养参数的标准化对于获得更强的再现性并提高数据的相关性至关重要。实际上，RPMI 2650屏障性质严重依赖于细胞培养条件，特别是生理空气液体界面，其增强了紧密结蛋白和药物转运蛋白的表达。相反，细胞培养基和插入组合物对鼻屏障的四个关键参数显示出微小的影响。尽管近期RPMI 2650模型的生理表征近期的进展，但只有有限的药理学数据涉及吸毒者在药物生物利用度中的参与。需要使用参考化合物的标准化双向渗透性研究的部署来确定RPMI 2650模型在药物运输研究领域的相关性。

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