Fig. 9

Graphical representation of the complex biokinetics after the inhalation of 20 nm [¹⁰⁵Ag]AgNP. In step 1 freshly deposited [¹⁰⁵Ag]AgNP start dissolving thereby releasing Ag + ions from their surface. In step 2 a fraction of the ions form layers of Ag-salt molecules around the [¹⁰⁵Ag]AgNP which retards the further release of Ag⁺ ions from the NP surface (step 3). In step 4 the rest of the Ag + ions form [¹⁰⁵Ag]Ag-salt molecules of low solubility in the alveolar ELF which is rich in Cl⁻, S²⁻, PO₄²⁻ and Se²⁻ ions. Due to the high concentration of the [¹⁰⁵Ag]Ag-salt molecules, they precipitate to nano-sized clusters (step 5). The [¹⁰⁵Ag]Ag-salt clusters scavenge most of the [¹⁰⁵Ag]Ag-salt molecules (step 6). Both the cores of [¹⁰⁵Ag]AgNP and the [¹⁰⁵Ag]Ag-salt clusters are phagocytized by lung surface macrophages (step 7) which will gradually transport them to the distal end of the ciliated airways for mucociliary transport to the larynx where they are swallowed into the GIT (step 8). Alternatively both particulate species may be endocytosed by cells of the alveolar epithelium (e.g. epithelial type 1 + 2 cells, fibroblasts et.) which may exocytose them in exosomes for translocation across the ABB (step 9). Translocation across the ABB of both particulate species may also occur directly from the ELF as indicated by the arrows of translocation. Hence this series of steps highlights the fate of [¹⁰⁵Ag]AgNP and their degradation products, which results in the clearance of two slowly dissolving particle species – persistent cores of [¹⁰⁵Ag]AgNP and clusters of low solubility [¹⁰⁵Ag]Ag-salt. Once arrived in the blood both particulate species may accumulate in secondary organs and tissues as indicated schematically by liver, spleen, and kidneys and discussed below. Note that we focus here on the alveolar epithelium due to our interest in long-term particle clearance. We hypothesize that steps 1 to 6 are similarly occurring in the airway epithelium leading predominantly to mucociliary clearance