Prior Projects

Principal Investigator

Olivier Jolliet

Additional Personnel

Yvan Wenger

About this Project

This projects aims to develop a physiologically based pharmacokinetics (PBPK) model that has been calibrated using experimental measurements of biodistribution and excretion of polyacrylamide nanoparticles in rats after a single i.v. injection. Nanoparticles analyzed here have a mean diameter of 60nm, are composed of a polyacrylamide core matrix that can be filled with active agents, and targeted to designated locations. This study elucidates the types of kinetic involved in the distribution, excretion, and saturation processes using physiologically relevant parameters. Distribution to the organs of the reticular endothelium system is rapid and saturable, making the fraction captured dose-dependent. The liver is the organs containing the greatest amount of macrophages, and is largely dominating the mass of accumulated nanoparticles in organs. Consistently with anatomical features of the kidney, most of the excretion through urine occurs shortly after injection and is not dependent of the total concentration of nanoparticles in blood. In an opposite manner, excretion in faeces is slow and proportional to the blood concentration. Overall, excretion through urine and faeces are not major routes of eliminations since they only account for ~5% of the injected dose (after 120hr). Finally, first order transfers from the blood to the carcass, characterized by a slower kinetic of accumulation when compared to the organs, can be responsible for the majority of the sequestration of nanoparticles after 120hr when the dose exceeds the capture capacity of the organs. The model allows predicting that accumulation in peripheral tissues would be significantly lower if the dose was not sufficient to saturate the organs. In a more general way, this model set the basis for exploring scaling as well as identifying key factors affecting the body distribution of this type of nanoparticles.