Summary
Xenobiotic aerosols may be delivered to the respiratory tract either intentionally, as in the case of drug delivery to the lung or unintentionally through the inhalation of environmental or occupational pollutants. An understanding of xenobiotic permeability and subsequent bioavailability is of critical concern in both scenarios, either for drug development or risk assessment purposes related to environmental exposure and occupational safety. With regards to the latter there is currently a lack of well-accepted in vitro models for the quantitative prediction of systemic bioavailability with some guidelines stating it must be assumed that 100% of the inhaled xenobiotic is systemically absorbed. This study aimed to compare the Parallel Artificial Membrane Permeability Assay (PAMPA) to human respiratory epithelial cell lines for the estimation of permeability of aerosolised xenobiotics. In addition to PAMPA, with the aim of modelling different regions of the respiratory tract, RPMI-2650, Calu-3, A549 and TT1 were used to represent the nasal, bronchial and alveolar regions of the respiratory tract, respectively. Three test compounds commonly used to measure permeability were selected; Sodium fluorescein, Rhodamine-123 and FITC-Dextran 4000. With all three test compounds, the PAMPA model presented a significantly greater permeability barrier than any of the cell layers, with the exception of Calu-3. Whilst the use of epithelial cell lines remains of crucial importance particularly for the investigation of active transport and facilitated diffusion, the development or optimisation of a “lung” PAMPA model, would be of considerable benefit to modelling passive transport due to reduced time, variability and cost compared to cell models.
Key Message
PAMPA and human epithelial cell were evaluated as experimental models for estimating xenobiotic permeability in the respiratory tract. This may aid current efforts to use in vitro data to inform computational modelling of inhaled xenobiotic absorption either for drug delivery or environmental/occupational exposure to air pollutants.
