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Efficient bioactive delivery of aerosolized drugs to human pulmonary epithelial cells cultured at air-liquid interface conditions.
Am. J. Respir. Cell Mol. Biol. 51, 526-535 (2014)
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 drugs in the medium completely covering the cells which represents an unphysiological drug application scenario. While physiologically realistic in vitro cell culture models of the pulmonary air-blood barrier are available, reliable, easy-to-handle and efficient technologies for direct aerosol-to-cell delivery are lacking. Here, we introduce the ALICE-CLOUD technology, which utilizes principles of cloud motion for fast and quantitative delivery of aerosolized liquid drugs to pulmonary cells cultured under realistic air-liquid interface conditions. Aerosol-to-cell delivery proved to be highly efficient, reproducible and rapid when using aerosolized fluorescein as surrogate drug. As a proof-of-concept study for the ALICE-CLOUD we performed functional efficacy studies with the FDA-approved proteasome inhibitor Bortezomib, a novel candidate drug for inhalation therapy. Aerosolized Bortezomib had a pronounced anti-inflammatory effect on human epithelial lung cells (A549) as indicated by a significant reduction of (TNFα-induced) IL-8 promoter activation. Importantly, cell-based therapeutic efficacy of aerosolized Bortezomib at air-liquid interface conditions was similar to dissolved and non-aerosolized submerged conditions, but with faster uptake kinetics. Our data indicate that the ALICE-CLOUD is a reliable tool for aerosolized drug screening with cells cultured at air-liquid interface conditions, which combines ease-of-handling with rapid, efficient and dosimetrically accurate drug-to-cell delivery. This may pave the way for screening of inhalable drugs under physiologically more relevant and hence potentially more predictive conditions than the currently used submerged cell culture systems.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
aerosolized drug delivery; air-liquid interface (ALI) and submerged cell culture; lung epithelial cell (A549, 16HBE14o-); proteasome inhibitor; inflammation; Human Lung-cells; In-vitro Model; Respiratory-tract; Exposure; Deposition; Particles; Nanoparticles; Surfactant; System; Inhibition
ISSN (print) / ISBN
1044-1549
e-ISSN
1535-4989
Quellenangaben
Volume: 51,
Issue: 4,
Pages: 526-535
Publisher
American Thoracic Society
Publishing Place
New York
Non-patent literature
Publications
Reviewing status
Peer reviewed