Is RPMI 2650 a Suitable In Vitro Nasal Model for Drug Transport Studies?

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.