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Pharmacokinetics, tissue distribution and excretion of polyacrylamide nanoparticle

M. Philbert, Y. Wenger, R. Schneider and O. Jolliet
University of Michigan, US

Keywords:
nanoparticle, polyacrylamide, toxicokinetics, tissue distribution

Abstract:
This paper presents a multi-compartmental pharmacokinetics model as well as experimental measurements of biodistribution and excretion pathways of polyacrylamide nanoparticle following an intravenous administration. The study was carried out on various type of particle including polyacrilamyde (PAA), polyethylene-glycol-coated polyacrilamyde (PAApeg) as well as biodegradable PAA synthesized with 10%, 15% and 20% of glycerol, a degradable cross linker. Non degradable PAA and PAApeg exhibit residence time in plasma of t1/2=24 h, partitioning equally in plasma and whole blood with little affinity to RBC’s. Tissue distribution shows the largest percent of nanoparticle in the liver, with a constant accumulation over time. Excretion and whole carcass data indicate that >95% of the administrated dose of non degradable PAA remains in the body after 120hrs, indicating a significant tendency for accumulation. The degradable PAA exhigit bi-exponential kinetics (t1/2=16-24 h; t1/2=230-300 h). Differential excretion profiles indicate that the clearance of the nanoparticles is bi-phasicduring the 42 days interval, with the greatest amount excreted in the first 24h, followed by a decrease for 14 days and an increase in a second phase thereafter. These experiments and the pharmacokinetic model set the basis for exploring scaling as well as identifying key factors affecting the pharmacokinetics of nanoparticles.

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