Clearance of nanoparticles from blood: effects of hydrodynamic size and surface coatings

Abstract

The distribution of nanoparticles (NPs) in the human body is associated with the development of nano-medicines and nanotoxicity. Physiologically based pharmacokinetic (PBPK) tools can simulate the distribution and elimination of NPs but are primarily dependent on experimental data. Models involving NP size and surface coating as parameters for estimating the clearance of NPs from blood are beneficial to the extension application of PBPK models. To this end, we first collected intravenous kinetic data on the blood distribution of 19 types of NPs for model parameterization and then collected 20 types of NPs for validation. Rate constants for clearance from blood were obtained by fitting the collected data to one- and two-compartment kinetics. A generic model (NP size-based) for estimation of rate constants was developed based on collision and diffusion behavior driven by NP size. NPs with a hydrodynamic diameter of 20 nm have the highest clearance rate constant via penetration and phagocytosis pathways. An extended model (NP size- and surface coating-based) was built to estimate rate constants of various NPs by calculating van der Waals energy between NPs and macrophages. Nearly 3/4 of the validation data are within 95% confidence intervals, indicating that our generic and extended models can be applied to NPs with different sizes and surface modifications.