In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration

Biomaterials. 2013 Apr;34(11):2787-95. doi: 10.1016/j.biomaterials.2013.01.001. Epub 2013 Jan 20.

Abstract

Graphene oxide (GO) and its functionalized derivatives have attracted great attention in biomedicine in recent years. A number of groups including ours have studied the in vivo behaviors of functionalized nano-graphene after intravenous injection or inhalation, and uncovered the surface coating & size dependent biodistribution and toxicology profiles for this type of nanomaterials. However, the fate of GO derivatives in animals after oral feeding and intraperitoneal (i.p.) injection, which are two other major drug administration routes, remain unclear. Therefore, in this work, we sought to systematically investigate in vivo biodistribution and potential toxicity of as-made GO and a number of polyethylene glycol (PEG) functionalized GO derivatives with different sizes and surface coatings, after oral and intraperitoneal administration at high doses. It is found that (125)I labeled PEGylated GO derivatives show no obvious tissue uptake via oral administration, indicating the rather limited intestinal adsorption of those nanomaterials. In contrast, high accumulation of PEGyalted GO derivatives, but not as-made GO, in the reticuloendothelial (RES) system including liver and spleen is observed after i.p. injection. Further investigations based on histological examination of organ slices and hematological analysis discover that although GO and PEGylated GO derivatives would retain in the mouse body over a long period of time after i.p. injection, their toxicity to the treated animals is insignificant. Our work is an important fundamental study that offers a deeper understanding of in vivo behaviors and toxicology of functionalized nano-graphene in animals, depending on their different administration routes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Female
  • Graphite / pharmacokinetics
  • Graphite / toxicity*
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred BALB C
  • Nanostructures / toxicity*
  • Oxides / pharmacokinetics
  • Oxides / toxicity*
  • Polyethylene Glycols
  • Tissue Distribution

Substances

  • Oxides
  • Polyethylene Glycols
  • Graphite