A Hand-Held Apparatus for “Nose-Only” Exposure of Mice to Inhalable Microparticles as a Dry Powder Inhalation Targeting Lung and Airway Macrophages

Abstract

A hand-held apparatus designed for the purpose of administering dry powder inhalations to rodents by “Nose-only” exposure was standardized. An aerosol of microparticles containing the anti-tuberculosis drugs isoniazid and rifabutin was generated and the dose available for inhalation by rodents was determined by collecting microparticles emitted at the delivery port. Separate groups of mice received inhalations of microparticles, free rifabutin orally, or free rifabutin intravenously. Rifabutin was estimated in serum and tissues by HPLC. When ~20 mg of microparticles were loaded in the apparatus, ~2.5 mg were collected at the delivery port in 30 seconds of operation. Mice inhaled ~300 g of the 2.5 mg emitted at the delivery port. Alveolar macrophages of mice receiving inhalations for 30 sec accumulated 0.38 μg of rifabutin, while the amount in blood serum of these mice was 0.62 μg. In mice receiving 83 g rifabutin intravenously or orally, the intracellular amounts were 0.06 and 0.07 μg respectively, while the amounts in serum were 1.02 and 0.80 μg. These observations confirmed that inhalation of microparticles targeted lung macrophages. The dose available for inhalation was consistent with the duration of exposure (10.5-13.5 CV%) and its dependence on the amount of microparticles loaded (r2=0.982), and on duration of exposure (r2=0.992), was satisfactory.