A Novel Method to Aerosolize Powder for Short Inhalation Exposures at High Concentrations: Isolated Rat Lungs Exposed to Respirable Diesel Soot

Abstract

More efficient methods are needed to aerosolize dry powders for short-duration inhalation exposures at high concentrations. There is an increasing need to reach the peripheral lung with dry powder medications as well as with collected ambient aerosol particulates in environmental research projects. In a novel aerosol generator, a fixed volume of compressed air was used to create a short burst of a highly concentrated aerosol in a 300-ml holding chamber. Collected diesel soot was deagglomerated to a fine aerosol with a mass median aerodynamic diameter (MMAD) of 0.55 μm, not much larger than the 0.25 μm MMAD of diesel exhaust particles measured in air. A fine powder such as 3-μm silica particles was completely deagglomerated to an aerosol with a MMAD of 3.5 μm. Immediately after generation, the aerosol was available for exposure at a chosen flow rate by the use of an automated valve system. Tritium-labeled diesel soot was thus used to expose the isolated perfused rat lung at an air concentration of ∼3 mg/L and a flow rate of 370 ml/min in a 1-min-long exposure. The lungs were ventilated at 75 breaths/min and a tidal volume of 1.13 ± 0.11 ml (SD, n = 3). Results showed that 19.8 ± 1.1 μg (SD, n = 3) soot was deposited in the lungs. This amount constitutes 9.5% of the amount inhaled and is close to literature data on deposition of similar sized particles in the rat lung. More than 97% of the deposited soot was located distal to the extrapulmonary bronchi, indicating that the system delivers a highly respirable aerosol. The aerosol system is particularly useful for peripheral lung delivery of collected ambient aerosols or dry powder pharmaceuticals following a minimal effort in formulation of the powder.

Research supported by the Swedish Agency for Innovation Systems (Vinnova) and the Swedish Council for Working Life and Social Research (FAS). The experiments were approved by the local ethics committee at Karolinska Institutet.