Bile salt enhancers for inhalation:Correlation between in vitro and in vivo lung effects
| Autor: | Ismo K. Koponen, Rebecca Fransson, Jorid B. Sørli, Yi Y. Zuo, Emilie Da Silva, Karin Sørig Hougaard, Kinga Balogh Sivars, Ingrid E.K. Weydahl, Per M. Åberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine MucilAirTM Lung surfactant Pharmaceutical Science Pharmacology Bile salt 030226 pharmacology & pharmacy Epithelium Bile Acids and Salts Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Pulmonary surfactant In vivo Administration Inhalation Respiration medicine Animals Lung Inhaled pharmaceutical enchancer Aerosols Inhalation Chemistry Constrained drop surfactometer Pulmonary Surfactants respiratory system 3D human airway in vitro model In vitro respiratory tract diseases 030104 developmental biology medicine.anatomical_structure MucilAir (TM) Alternative method Drug delivery Inhaled pharmaceutical enhancer |
| Zdroj: | Sorli, J B, Sivars, K B, Da Silva, E, Hougaard, K S, Koponen, I K, Zuo, Y Y, Weydahl, I E K, Aberg, P M & Fransson, R 2018, ' Bile salt enhancers for inhalation : Correlation between in vitro and in vivo lung effects ', International Journal of Pharmaceutics, vol. 550, no. 1-2, pp. 114-122 . https://doi.org/10.1016/j.ijpharm.2018.08.031 Sørli, J B, Sivars, K B, Da Silva, E, Hougaard, K S, Koponen, I K, Zuo, Y Y, Weydahl, I E K, Åberg, P M & Fransson, R 2018, ' Bile salt enhancers for inhalation: correlation between in vitro and in vivo lung effects ', International Journal of Pharmaceutics, vol. 550, no. 1-2, pp. 114-122 . https://doi.org/10.1016/j.ijpharm.2018.08.031 |
| Popis: | The lungs have potential as a means of systemic drug delivery of macromolecules. Systemic delivery requires crossing of the air-blood barrier, however with molecular size-dependent limitations in lung absorption of large molecules. Systemic availability after inhalation can be improved by absorption enhancers, such as bile salts. Enhancers may potentially interfere with the different constituents of the lungs, e.g. the lung surfactant lining the alveoli or the lung epithelium. We used two in vitro models to investigate the potential effects of bile salts on lung surfactant function (with the constrained drop surfactometer) and on the epithelium in the proximal airways (with the MucilAirTM cell system), respectively. In addition, we measured direct effects on respiration in mice inhaling bile salt aerosols. The bile salts inhibited lung surfactant function at different dose levels, however they did not affect the integrity of ciliated cells at the tested doses. Furthermore, the bile salt aerosols induced changes in the breathing pattern of mice indicative of pulmonary irritation. The bile salts were ranked according to potency in vitro for surfactant function disruption and in vivo for induction of pulmonary irritation. The ranking was the same, suggesting a correlation between the interference with lung surfactant and the respiratory response. |
| Databáze: | OpenAIRE |
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