Development of an in vitro exposure model for investigating the biological effects of therapeutic aerosols on human cells from the respiratory tract.
Respiratory diseases like asthma or COPD are gaining more and more importance worldwide due to an increased exposure of humans to inhalable compounds such as cigarette smoke, diesel exhaust or other forms of environmental pollution. Therefore, a high impact on national health systems is expected, meaning long-term treatment, with periodic examinations accompanied by high costs. Although a number of efficient drugs for these disease patterns, like Tiotropium (antimuscarinic), Salmetron (β-antagonist) or corticosteroids, are already available, a great deal of effort has to be put into the development of new drugs and therapy concepts. In this context, in vitro methods may be useful to establish more efficient prescreening procedures to analyze, for example, the toxicity of new compounds during the research and development process. These studies should aim to achieve a better selection of substances relevant for further development and a final reduction in the number of animal experiments. Therefore, we established an in vitro exposure device that allows the analysis of inhalable compounds for their pharmacological and toxicological effects. This CULTEX(®) device is composed of an exposure entity representing the in vivo respiratory air compartment and a basal feeding compartment representing the subepithelium. Both compartments are connected by porous transwells on which cells form an epithelium-like cell layer. We have used this system for exposing human lung cells directly to liquid aerosols and present the first data with regard to aerosolized model substances.
Deschl
U
U
Boehringer Ingelheim, Pharma GmbH & Co. KG, Department Nonclinical Drug Safety, Birkendorferstrasse 65, 88397 Biberach an der Riss, Germany.
Vogel
J
J
Aufderheide
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D006801:Humans; D008954:Models, Biological; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects*
D000336:Aerosols; D001993:Bronchodilator Agents; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate