Biodistribution of Inhaled Gold Nanoparticles in Mice and the Influence of Surfactant Protein D

Background: 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. Methods: Aerosolized 20-nm radioactively labeled Au NP were inhaled by healthy adult female mice. One group of mice received dissolved 10 mu g 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. Results: 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. Conclusion: 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.