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- W2800178146 abstract "The RPMI 2650 cell line has been described as a potent model of the human nasal mucosa. Nevertheless, pharmacological data are still insufficient, and the role of drug efflux transporters has not been fully elucidated. We therefore pursued the pharmacological characterization of this model, initially investigating the expression of four well-known adenosine triphosphate [ATP]-binding cassette (ABC) transporters (P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)1, MRP2, and breast cancer resistance protein (BCRP)) by means of ELISA and immunofluorescence staining. The functional activity of the selected transporters was assessed by accumulation studies based on specific substrates and inhibitors. We then performed standardized bidirectional transport experiments under air–liquid interface (ALI) culture conditions, using four therapeutic compounds of local intranasal relevance in upper airway diseases. Protein expression of P-gp, MRP1, MRP2, and BCRP was detected at the membrane of the RPMI 2650 cells. In addition, all four transporters exhibited functional activity at the cellular level. In the bidirectional transport experiments, the RPMI 2650 model was able to accurately discriminate the four therapeutic compounds according to their physicochemical properties. The ABC transporters tested did not play a major role in the efflux of these compounds at the barrier level. In conclusion, the RPMI 2650 model represents a promising tool for assessing the nasal absorption of drugs on the basis of preclinical pharmacological data." @default.
- W2800178146 created "2018-05-17" @default.
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- W2800178146 date "2018-04-30" @default.
- W2800178146 modified "2023-10-16" @default.
- W2800178146 title "Pharmacological Characterization of the RPMI 2650 Model as a Relevant Tool for Assessing the Permeability of Intranasal Drugs" @default.
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- W2800178146 doi "https://doi.org/10.1021/acs.molpharmaceut.8b00087" @default.
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