Is the cellular uptake of respiratory aerosols delivered from different devices equivalent?
The study focuses on the application of a cell integrated modified Andersen Cascade Impactor (ACI) as an in vitro lung model for the evaluation of aerosols' behaviour of different formulation devices, containing the same active drug, specifically nebuliser, pressurised metered dose inhaler (pMDI) and dry powder inhaler (DPI). Deposition and transport profiles of the three different inhaled salbutamol sulphate (SS) formulations with clinically relevant doses were evaluated using a modified ACI coupled with the air interface Calu-3 bronchial cell model. Reproducible amounts of SS were deposited on Snapwells for the different formulations, with no significant difference in SS deposition found between the standard ACI plate and modified plate. The transport of SS aerosols produced from pMDI formulation had similar transport kinetics to nebulised SS but significantly higher compared to the DPI, which could have led to the differences in clinical outcomes. Furthermore, drug absorption of different inhaled formulation devices of the same aerodynamic fraction was found not to be equivalent due to their physical chemical properties upon aerosolisation. This study has established an in vitro platform for the evaluation of the different inhaled formulations in physiologically relevant pulmonary conditions.
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia. Electronic address: hong3117@uni.sydney.edu.au.
Hui Xin
HX
Ong
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia.
Daniela
D
Traini
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia.
Ching-Yee
CY
Loo
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia.
Lala
L
Sarkissian
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
Gianluca
G
Lauretani
Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
Santo
S
Scalia
Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, NSW 2037, Sydney, Australia; Discipline of Pharmacology, Sydney Medical School, University of Sydney, NSW 2000, Australia.
Paul M
PM
Young
D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D058995:Dry Powder Inhalers; D004847:Epithelial Cells / Q000378:metabolism*; D004867:Equipment Design; D006801:Humans; D036501:Metered Dose Inhalers; D010316:Particle Size; D011208:Powders; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods
D000336:Aerosols; D001993:Bronchodilator Agents; D011208:Powders; D000420:Albuterol
Andersen cascade impactor; Calu-3; DPI; Inhaled formulation; Nebuliser; Salbutamol; pMDI