Modeling Interorgan Distribution and Bioaccumulation of Engineered Nanoparticles (Using the Example of Silver Nanoparticles)

In this paper we demonstrate the validity of a mathematical chamber model to describe the absorption, distribution, and bioaccumulation of nonmetabolizable nanoparticles (NPs) using the example of silver NPs in the organism of laboratory rat. The model is constructed using experimental data on the bioaccumulation and biodistribution of silver NPs of average diameter of 35 +/- 15 nm (M +/- SD) radiolabeled with Ag-110m. In the minimally acceptable form, the model includes all chambers in which NP level in the course of the experiment was no lower than 20-25% of its blood content, namely, the gastrointestinal tract (GIT), blood itself, osteomuscular carcass, liver, and spleen. NP bioaccumulation and biodistribution in these chambers is described by five independent linear differential equations of the 1st order. A numerical solution of this system of equations, with account for the data on timing of NP excretion from the GIT in the content of feces, makes it possible to determine the biokinetic rate constants for the interorgan transfer of NPs. These rate constants are used to establish the dose-dependence of the peak (maximum) and quasi-stationary NP content in critical target organs, respectively, in the case of acute (single) and subchronic (repeated) administration of NP in the gastrointestinal tract. The results justify the value of the method of mathematically modeling the interstitial transport and distribution of NPs to assess their potential toxic effects on a system level using previously obtained in vitro data and results from biokinetic studies.