The Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) in vitro system: design and experimental protocol.
The development of aerosol medicines typically involves numerous tests on animals, due to the lack of adequate in vitro models. A new in vitro method for testing pharmaceutical aerosol formulations on cell cultures was developed, consisting of an aerosolisation unit fitting a commercial dry powder inhaler (HandiHaler(c), Boehringer Ingelheim, Germany), an air-flow control unit (Akita(c), Activaero, Germany) and a custom-made sedimentation chamber. This chamber holds three Snapwell(c) inserts with monolayers of pulmonary epithelial cells. The whole set-up, referred to as the Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) system, aims to mimic the complete process of aerosol drug delivery, encompassing aerosol generation, aerosol deposition onto pulmonary epithelial cells and subsequent drug transport across this biological barrier, to facilitate the investigation of new aerosol formulations in the early stages of development. We describe here, the development of the design and the protocol for this device. By testing aerosol formulations of budesonide and salbutamol sulphate, respectively, reproducible deposition of aerosol particles on, and the integrity of, the pulmonary cell monolayer could be demonstrated.
Hein
Stephanie
S
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
Bur
Michael
M
Kolb
Tobias
T
Muellinger
Bernhard
B
Schaefer
Ulrich F
UF
Lehr
Claus-Michael
CM
D000336:Aerosols; D000826:Animal Testing Alternatives / Q000295:instrumentation / Q000379:methods*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002478:Cells, Cultured / Q000166:cytology / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004867:Equipment Design; D006801:Humans; D015203:Reproducibility of Results
D000336:Aerosols