Hemoglobin-based oxygen carrier microparticles: synthesis, properties, and in vitro and in vivo investigations

Biomacromolecules. 2012 Oct 8;13(10):3292-300. doi: 10.1021/bm301085x. Epub 2012 Sep 25.

Abstract

Bovine hemoglobin microparticles (Hb-MPs) as suitable oxygen carriers are fabricated easily by three key steps: coprecipitation of Hb and CaCO(3) to make Hb-CaCO(3)-microparticles (Hb-CaCO(3)-MPs), cross-linking by glutaraldehyde (GA) to polymerize the Hb and dissolution of CaCO(3) template to obtain pure Hb-MPs. The Hb entrapment efficiency ranged from 8 to 50% corresponding to a hemoglobin quantity per Hb-MP of at least one-third of that in one erythrocyte. The Hb-MPs are spherical, with an average diameter of 3.2 μm and high oxygen affinity. The methemoglobin level was increased after preparation, but can be reduced to less than 7% with ascorbic acid. Phagocytosis assays showed low immunogenicity of Hb-MPs if the particles were cross-linked with low concentration of GA and treated with sodium borohydride. Magnetite-loaded Hb-MPs circulated up to 4 days after intravenous application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Carbonate / blood
  • Calcium Carbonate / chemistry
  • Calcium Carbonate / pharmacokinetics
  • Cattle
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / metabolism
  • Cross-Linking Reagents / pharmacokinetics*
  • Glutaral / blood
  • Glutaral / chemistry
  • Glutaral / pharmacokinetics
  • Hemoglobins / chemistry
  • Hemoglobins / metabolism
  • Hemoglobins / pharmacokinetics*
  • Magnetic Resonance Imaging
  • Oxygen / blood
  • Oxygen / chemistry*
  • Particle Size
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Cross-Linking Reagents
  • Hemoglobins
  • Calcium Carbonate
  • Oxygen
  • Glutaral