Pharmaceutical aerosol deposition device on cell cultures (PADDOCC) : development of an in vitro test system based on pulmonary epithelial cells

摘要

Drug application via the lung is a convenient route of administration, because of its easy handling and the special anatomy of the lung. A large surface area, rapid absorption through the thin alveolar epithelium, low enzymatic activity and a direct access to the blood circulation are the advantages of the administration of local as well as systemic drugs to the lung. However, new drugs and formulations have to be tested for their safety and efficacy, especially since new particle types like nanoparticles or liposomes arein the focus of the development of new drugs. Such testing is often done by animal experiments due to a lack of appropriate in vitro models. Therefore a new in vitro model was developed allowing to test aerosolisation, deposition as well as subsequent absorption of aerosol formulations. The so-called "Pharmaceutical Aerosol Deposition Device On Cell Cultures" (PADDOCC) system relies on sedimentation, which is the main deposition mechanism in the deep lung. The PADDOCC system, comprising of air flow control unit, aerosolisation unit and deposition unit, is able to generate the dry powder aerosol and deposit only the respirable fraction simultaneously onto three air-liquid interface grown cell monolayers. After the deposition several endpoints such as cytotoxicity or absorption are determined. Budesonide and salbutamol sulphate, two important drugs, which are used to treat asthma were tested, and dierent absorption prfiles compared to standardised transport studies could be detected.