AUTHOR=Horstmann Justus C. , Thorn Chelsea R. , Carius Patrick , Graef Florian , Murgia Xabier , de Souza Carvalho-Wodarz Cristiane , Lehr Claus-Michael 

TITLE=A Custom-Made Device for Reproducibly Depositing Pre-metered Doses of Nebulized Drugs on Pulmonary Cells in vitro

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.643491

DOI=10.3389/fbioe.2021.643491

ISSN=2296-4185

ABSTRACT=The deposition of pre-metered (i.e., defined before and not after exposition) doses at the air-liquid interface of viable pulmonary epithelial cells remains an important but challenging task when using such models for developing aerosol medicines. While some devices allow quantification of the deposited dose after or during the experiment, e.g., gravimetrically, there is still no generally accepted way to deposit small pre-metered doses of aerosolized drugs or pharmaceutical formulations, e.g., nanomedicines. Here, we describe a straight-forward custom-made device, allowing to connect commercially available nebulizers with standard cell culture plates. Designed to tightly fit into the approximately 12 mm opening of either a 12-well Transwell® insert or a single 24-well, a defined dose of an aerosolized liquid can be directly deposited precisely and reproducibly (4.8 % deviation) at the air-liquid interface (ALI) of pulmonary cell cultures. The deposited dose can be controlled by the volume of the nebulized solution, which may vary in a range from 20 to 200 µL. The entire nebulization-deposition maneuver is completed after 30 s and is spatially homogenous. After PBS deposition, the viability and barrier properties (transepithelial electrical resistance) of human bronchial epithelial Calu-3 cells were not negatively affected. Straight-forward in manufacture and use, the device enables reproducible deposition of metered doses of aerosolized drugs to study the interactions with pulmonary cell cultures grown at ALI conditions.