Gerde Per, Ewing Pär, Låstbom Lena, Ryrfeldt Ake, Waher Juri, Lidén Göran
National Institute of Environmental Medicine, Division of Lung Physiology, Karolinska Institutet, Stockholm, Sweden.
Inhal Toxicol. 2004 Jan;16(1):45-52. doi: 10.1080/08958370490258381.
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 microm, not much larger than the 0.25 microm MMAD of diesel exhaust particles measured in air. A fine powder such as 3-microm silica particles was completely deagglomerated to an aerosol with a MMAD of 3.5 microm. 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 approximately 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 microg (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.
需要更有效的方法来雾化干粉，以用于高浓度的短期吸入暴露。在环境研究项目中，使用干粉药物以及收集的环境气溶胶颗粒到达外周肺的需求日益增加。在一种新型气溶胶发生器中，使用固定体积的压缩空气在一个300毫升的容纳腔中产生一阵高浓度的短时间气溶胶。收集的柴油烟灰被解聚成细气溶胶，其质量中值空气动力学直径（MMAD）为0.55微米，比在空气中测量的柴油尾气颗粒的0.25微米MMAD大不了多少。诸如3微米二氧化硅颗粒这样的细粉完全解聚成MMAD为3.5微米的气溶胶。生成后，立即通过使用自动阀门系统以选定的流速提供气溶胶用于暴露。因此，使用氚标记的柴油烟灰以约3毫克/升的空气浓度和370毫升/分钟的流速在1分钟的暴露中对离体灌注大鼠肺进行暴露。肺以75次/分钟的呼吸频率和1.13±0.11毫升（标准差，n = 3）的潮气量进行通气。结果表明，19.8±1.1微克（标准差，n = 3）的烟灰沉积在肺中。这个量占吸入量的9.5%，并且接近关于类似大小颗粒在大鼠肺中沉积的文献数据。超过97%的沉积烟灰位于肺外支气管的远端，表明该系统可输送高度可吸入的气溶胶。该气溶胶系统对于在外周肺输送收集的环境气溶胶或干粉药物特别有用，只需对粉末进行最少的制剂工作。
