Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part II: evaluation of IL-10-loaded microparticles for the treatment of lung inflammation.
Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface. This treatment significantly reduced the secretion of interleukin-6 and tumour necrosis factor, as compared to the deposition of placebo (unloaded) particles. Our results show that the alveolar co-culture model, in combination with a deposition device such as the PADDOCC, may serve as a powerful tool for testing the safety and efficacy of dry powder formulations for pulmonary drug delivery.
PharmBioTec GmbH, Saarbrücken, Germany and Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Marius
M
Hittinger
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany and Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Nico Alexander
NA
Mell
Heart and Thoracic Surgery, SHG Kliniken Völklingen, Saarbrücken, Germany.
Hanno
H
Huwer
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Brigitta
B
Loretz
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 / Q000494:pharmacology*; D000826:Animal Testing Alternatives; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000494:pharmacology*; D008171:Lung Diseases / Q000188:drug therapy; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D018675:Toxicity Tests / Q000379:methods*
D000336:Aerosols; D016207:Cytokines; D016753:Interleukin-10