Efficient Bioactive Delivery of Aerosolized Drugs to Human Pulmonary Epithelial Cells Cultured in Air–Liquid Interface Conditions

摘要: In inhalation therapy, drugs are deposited as aerosols onto the air-facing lung epithelium. The currently used in vitro cell assays for drug testing, however, typically dissolve medium, completely covering cells, which represents an unphysiological application scenario. Although physiologically realistic culture models of pulmonary air-blood barrier available, reliable, easy-to-handle, and efficient technologies direct aerosol-to-cell delivery lacking. Here, we introduce Air-Liquid Interface (ALI) Cell Exposure-Cloud (ALICE-CLOUD) technology, uses principles cloud motion fast quantitative aerosolized liquid to cells cultured under ALI conditions. Aerosol-to-cell proved be highly efficient, reproducible, rapid when using fluorescein surrogate drug. As a proof-of-concept study ALICE-CLOUD, performed functional efficacy studies with U.S. Food Drug Administration-approved proteasome inhibitor, Bortezomib, novel candidate therapy. Aerosolized Bortezomib had pronounced anti-inflammatory effect on human epithelial (A549), indicated by significant reduction (TNFα-induced) IL-8 promoter activation. Importantly, cell-based therapeutic conditions was similar that dissolved nonaerosolized submerged conditions, but faster uptake kinetics. Our data indicate ALICE-CLOUD is reliable tool screening combines ease handling rapid, dosimetrically accurate drug-to-cell delivery. This may pave way inhalable more relevant and, hence, potentially predictive than systems.