Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study. In the alveolar space of the lung, epithelial cells and alveolar macrophages are the most important cell types, forming an efficient cellular barrier to aerosols. Our aim was to mimic this barrier with primary human alveolar cells. Cell densities of alveolar macrophages and epithelial cells, isolated from the same human donor, were optimised, with a focus on barrier properties. The combination of 300,000 epithelial cells/cm² together with 100,000 macrophages/cm² showed a functional barrier (transepithelial electrical resistance > 500Ω.cm²). This cell model was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures. The functionality of the in vitro system was investigated with spray-dried fluorescently labelled poly(lactic-co-glycolic) acid particles loaded with ovalbumin as a model drug.
PharmBioTec GmbH, Saarbrücken, Germany and Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Marius
M
Hittinger
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Kiel, Germany.
Julia
J
Janke
Heart and Thoracic Surgery, SHG Kliniken Völklingen, Saarbrücken, Germany.
Hanno
H
Huwer
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Kiel, Germany.
Regina
R
Scherließ
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Nicole
N
Schneider-Daum
PharmBioTec GmbH, Saarbrücken, Germany; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Claus-Michael
CM
Lehr
D000336:Aerosols / Q000008:administration & dosage / Q000494:pharmacology*; D000826:Animal Testing Alternatives; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000336:Aerosols; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid