Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat.
A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles (~31 nm average diameter). PAA NPs and polyethylene glycol-coated PAA NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 min to 120 h and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43 h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120 h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000%-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non-pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage.
Risk Science Center, Department of Environmental Health Sciences, 109 S Observatory, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA. yvan@umich.edu
Yvan
Y
Wenger
Randal J
RJ
Schneider
G Ramachandra
GR
Reddy
Raoul
R
Kopelman
Olivier
O
Jolliet
Martin A
MA
Philbert
D000180:Acrylic Resins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D019540:Area Under Curve; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008962:Models, Theoretical; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute; D000099166:Polyacrylamides
D000180:Acrylic Resins; D004337:Drug Carriers; D011092:Polyethylene Glycols; D000099166:Polyacrylamides