Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration

Eur J Pharm Biopharm. 2011 Apr;77(3):407-16. doi: 10.1016/j.ejpb.2010.12.029. Epub 2010 Dec 31.

Abstract

Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment. We administered (198)Au-radio-labelled monodisperse, negatively charged GNP of five different sizes (1.4, 5, 18, 80, and 200 nm) and 2.8 nm GNP with opposite surface charges by intravenous injection into rats. After 24h, the biodistribution of the GNP was quantitatively measured by gamma-spectrometry. The size and surface charge of GNP strongly determine the biodistribution. Most GNP accumulated in the liver increased from 50% of 1.4 nm GNP to >99% of 200 nm GNP. In contrast, there was little size-dependent accumulation of 18-200 nm GNP in most other organs. However, for GNP between 1.4 nm and 5 nm, the accumulation increased sharply with decreasing size; i.e. a linear increase with the volumetric specific surface area. The differently charged 2.8 nm GNP led to significantly different accumulations in several organs. We conclude that the alterations of accumulation in the various organs and tissues, depending on GNP size and surface charge, are mediated by dynamic protein binding and exchange. A better understanding of these mechanisms will improve drug delivery and dose estimates used in risk assessment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gold Radioisotopes
  • Gold*
  • Injections, Intravenous
  • Liver / metabolism
  • Metabolic Clearance Rate
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Nanomedicine
  • Organ Specificity
  • Particle Size
  • Radioligand Assay
  • Rats
  • Rats, Inbred WKY
  • Spectrometry, Gamma
  • Surface Properties
  • Tissue Distribution

Substances

  • Gold Radioisotopes
  • Gold