A comparison of in vitro drug exposure modes: submerged versus ALI in the Vitrocell ® Cloud 24 aerosol exposure system

Abstract

Abstract In medical applications, inhalable drugs are commonly delivered as aerosols in which the drug is i) the only bioactive constituent and ii) confined to the particulate fraction. For these low complexity aerosols, there are indications that in vitro exposure at the air-liquid interface (ALI) does not increase in vitro-in vivo translatability compared to the less complex and more controlled exposures under submerged conditions. We characterized aerosol delivery within the Vitrocell® Cloud 24 an in vitro aerosol exposure system frequently used for conducting ALI exposures—and used the system to test the hypothesis that there are no relevant differences between exposure modes. Cultures of the human adenocarcinoma-derived cell line A549 were exposed to bortezomib, anatabine, or the selective IκB kinase IKK-16, either in submerged state or at the ALI. The drugs’ toxicities and efficacies to counteract an induced pre-inflammatory state were compared between the exposure modes. The impact of the complexity of the biological test system was investigated by including ALI exposures of organotypic bronchial epithelial cultures. Our results demonstrate that i) the Vitrocell® Cloud 24 is useful for conducting controlled aerosol exposures and ii) ALI and submerged exposures are not equivalent.