Lung delivery of aerosolized dextran.
The ability of nebulizers to deliver dextran (nominal molecular mass, 4,000 g/mol) to the lung as an inhaled aerosol is evaluated by in vitro experimental methods and mathematical models. Dextran in isotonic saline was aerosolized by four nebulizer types (Pari LC STAR, Hudson T-Updraft II, Acorn II, and Sonix 2000) at dextran concentrations </= 400 mg/ml and with 2.5- and 4-ml volume fills. Aerosols inhaled during breath simulation were characterized by in-line phase Doppler anemometry, filter collection, osmometry, and gravimetry. Mathematical models were used to estimate amounts of the characterized aerosols depositing in the different regions of lung models, and mathematical models of mucous thickness were then developed to estimate initial concentrations of the depositing dextran in the mucus of each conducting airway generation. Models of three subjects (4 yr old, 8 yr old, and adult) were used. The high viscosity of the dextran solutions tested (up to seven times that of water) negatively impacts nebulization, and results in poor performance with most delivery systems tested. Our results suggest that airway mucosal dextran concentrations associated with efficacy in previous animal and in vitro models are achievable with reasonable delivery times (</= 12 min) with only one of the delivery systems/formulations tested: the Pari LC STAR nebulizer, using a 2. 5-ml volume fill and a dextran concentration of 200 mg/ml.
Finlay
W H
WH
Aerosol Research Laboratory, Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada. warren.finlay@ualberta.ca
Lange
C F
CF
King
M
M
Speert
D P
DP
D000280:Administration, Inhalation; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism; D009330:Nebulizers and Vaporizers
D003911:Dextrans