Comprehensive Pneumology Center, Institute of Lung Biology and Disease and Focus Network NP and Health, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstäädter Landstraße 1, Neuherberg, Germany.
J Aerosol Med Pulm Drug Deliv. 2013 Feb;26(1):24-30. doi: 10.1089/jamp.2011.0951. Epub 2012 Aug 2.
The pulmonary route is very promising for drug delivery by inhalation. In this regard, nanoparticulate drug delivery systems are discussed, and one very promising nano carrier example is gold nanoparticles (Au NP). Directly after their deposition, inhaled Au NP come into contact with pulmonary surfactant protein D (SP-D). SP-D can agglomerate Au NP in vitro, and this may influence the clearance as well as the systemic translocation in vivo. The aim of the present study was to investigate the clearance and translocation of Au NP at a very early time point after inhalation, as well as the influence of SP-D.
Aerosolized 20-nm radioactively labeled Au NP were inhaled by healthy adult female mice. One group of mice received dissolved 10 μg of SP-D by intratracheal instillation prior to the Au NP inhalation. After a 2-hr Au NP inhalation period, the mice were killed immediately, and the clearance and translocation to the blood stream were investigated.
The highest amount of Au NP was associated with the lung tissue. In the bronchoalveolar lavage fluid (BALF), more Au NP remained free compared with the amount associated with the BALF cells. The amount of Au NP cleared by the mucociliary escalator was low, probably because of this very early time point. Instillation of SP-D prior to Au NP inhalation had no statistically significant effect on the biodistribution of the Au NP.
Our data show that inhaled Au NP are retained in the mouse lungs and are translocated after a short time, and that SP-D has only a minor effect on Au NP translocation and clearance at a very early time point.
肺部给药途径通过吸入非常有前途。在这方面,讨论了纳米颗粒药物传递系统,金纳米颗粒(AuNP)是一个非常有前途的纳米载体示例。吸入的 AuNP 直接沉积后,与肺表面活性蛋白 D(SP-D)接触。SP-D 可以在体外使 AuNP 聚集,这可能会影响清除率以及体内的系统转移。本研究的目的是研究吸入后非常早期 AuNP 的清除率和转移率,以及 SP-D 的影响。
通过健康成年雌性小鼠吸入气溶胶化的 20nm 放射性标记的 AuNP。一组小鼠在吸入 AuNP 之前通过气管内滴注接受溶解的 10μg SP-D。吸入 AuNP 2 小时后,立即处死小鼠,研究清除率和向血液系统的转移。
AuNP 与肺组织的关联量最高。在支气管肺泡灌洗液(BALF)中,与与 BALF 细胞相关的量相比,更多的 AuNP 保持游离状态。由于时间非常早,黏液纤毛清除器清除的 AuNP 量很少。在吸入 AuNP 之前滴注 SP-D 对 AuNP 的生物分布没有统计学上的显著影响。
我们的数据表明,吸入的 AuNP 保留在小鼠肺部并在短时间后转移,并且 SP-D 对 AuNP 转移和清除的早期影响很小。