In vivo measurement of extravasation of silver nanoparticles into liver extracellular space by push–pull-based continuous monitoring system

•An analytical system composed of PPP sampling, in-tube SPE, and ICP-MS was developed.•The system's detection limit and temporal resolution were 0.64 μg L−1 and 10 min.•The transport kinetics of extracellular AgNPs in rat liver was investigated in vivo.•Our results revealed the clearance of AgNPs may be blocked by a prior administration.

With the increasing prevalence of silver nanoparticles (AgNPs) in various products, whether such AgNPs will introduce new injury mechanisms from new pathologies remains to be determined. From the toxicokinetic viewpoint, it is vital to have in-depth knowledge of their in vivo transport kinetics and extravasation phenomenon. By combining push–pull perfusion sampling, in-tube solid phase extraction, and inductively coupled plasma mass spectrometry, we used an in vivo push–pull-based continuous monitoring system to investigate in vivo transport kinetics of extracellular AgNPs in living rat liver with a detection limit and temporal resolution of 0.64 μg L−1 and 10 min, respectively. Before administration into living rats, the pre-incubation in DMEM with 10% FBS for 8 h was adopted as the optimized exposure condition for the used AgNPs. After repeated-dose treatments, we observed a higher concentration of AgNPs in the liver extracellular space, suggesting that AgNP clearance by the reticuloendothelial system (RES) may be blocked by a prior administration of AgNPs. Future studies on AgNP distribution in different liver compartments (blood stream, extracellular space and Kupffer cells/hepatocytes) are necessary for defining the risks and benefits of AgNP applications.

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