Using a PBPK model to study the influence of different characteristics of nanoparticles on their biodistribution

Abstract

The studies on potential health risks possessed by engineered nanoparticles (NPs) have been growing rapidly. However, detailed and systemic knowledge on the uptake and biodistribution of NPs in body is still limited. Moreover, there is a need to characterize the relation between the characteristics of NPs (size, surface modifications, etc.) and their behaviours in the body. The aim of this study is to explore how these characteristics will influence the NPs uptake and biodistribution. We have successfully developed a Physiologically Based Pharmacokinetic (PBPK) model for the biodistribution of polyethylene glycol-coated polyacrylamide NPs in rats, modelling the capture and removal of NPs by phagocytizing cells. Based on this PBPK model, the behaviours of other nanoparticles (polymeric, quantum dot, silver, titanium oxide and cerium oxide NPs) are investigated, based on data from several experiments published in the literature. Size is one of the important properties to consider. Our model parameterization suggests that the uptake rate by phagocytizing cells will decrease as the size of nanoparticles increases when the removal rates for these nanoparticles are similar. This could indicate that the phagocytizing cells are saturated by the number of NPs rather than absolute mass. Nevertheless, surface modification, such as polyethylene glycol coating, may reduce the uptake rate by phagocytizing cells. With phagocytizing cells serving as a deposit of NPs, these influences of different characteristics of NPs to the behavior of phagocytizing cells could affect the fate of NPs in the body not only during the initial uptake within the first hour but also in long-term at the kinetic and dynamic levels.