AAAR 31st Annual Conference
October 8-12, 2012
Hyatt Regency Minneapolis
Minneapolis, Minnesota, USA
Abstract View
Evaluation of Drug Particle Deposition in Mouse Lung via Inhalation
JINGJIE ZHANG, Da-Ren Chen, Yian Wang, Washington University in St. Louis
Abstract Number: 274 Working Group: Health Related Aerosols
Abstract The inhalation of drug aerosols is one of administration routes for drug delivery, especially for the diseases in the respiratory tracts and the lung. The efficacy of a given drug via aerosol administration depends on many factors such as the particle size distribution, total particle mass concentration, and the physiochemical properties of drug particles. Genetically-engineered mice play an important role in drug screening and preclinical studies. Limited studies have been focused on particle deposition in mouse lungs. Because of much smaller dimension of the mouse respiratory system than human being’s, the deposition data obtained for human respiratory systems are not applied to the cases of mice. It is thus necessary to measure the mass deposition of particles in mouse lung.
In this study, Cisplatin-loaded polymer particles produced by aerosol generators were used. Cisplatin is an anticancer drug. Various polymers were also applied in the spray solutions to extend the retention time of Cisplatin in the mouse lung. We used electrospray aerosol generator to produce monodisperse drug particles of various sizes. For the comparison we also used Collison atomizer to generate polydisperse Cisplatin-loaded polymer particles. Generated particles were delivered to a custom-built nose-only exposure chamber and inhaled by the mice. The mice were sacrificed immediately after specified exposure time periods. The lungs of exposed mice were harvested and flash-frozen in liquid nitrogen lobe by lobe. The collected lung tissue samples were weighed and homogenized to extract Cisplatin. The extracted drug was then analyzed by ICP-MS. The deposition efficiency of drug particles was then derived from the mass measurement of Cisplatin contained in collected tissue samples for each mouse lung. At the same time, the size distributions of Cisplatin-loaded polymer particles were characterized via Scanning Mobility Particle Sizer (SMPS; TSI Inc). The airborne mass concentration of test particles in the exposure chamber was measured by a portable dust monitor (Kanomax, Model 3521). The result of this study will be given in this presentation.