Biochemical and aerosol characterization of ricin for use in non-clinical efficacy studies

J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21980. Epub 2017 Sep 7.

Abstract

Ricin toxin may be used as a biological warfare agent and no medical countermeasures are currently available. Here, a well-characterized lot of ricin was aerosolized to determine the delivered dose for future pre-clinical efficacy studies. Mouse intraperitoneal (IP) median lethal dose (LD50 ) bioassay measured potency at 5.62 and 7.35 μg/kg on Days 0 and 365, respectively. Additional analyses included total protein, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, and rabbit reticulocyte lysate activity assay. The nebulizer aerosol produced consistent concentrations (2.5 × 103 , 5.0 × 103 , 1.0 × 104 , and 1.5 × 104 μg/mL) and spray factor values. The aerosol particle size distribution was of sufficient size to deposit in lung alveoli (1.12-1.43 μm). Ricinus communis Agglutinin II (RCA 60), prepared at 19 mg/mL in phosphate-buffered saline, pH 7.8, and stored at -70°C, maintained attributes for toxicity following 1-year storage and aerosolized consistently.

Keywords: aerosol; characterization; potency; ricin; stability.

MeSH terms

  • Aerosols
  • Animals
  • Drug Evaluation, Preclinical
  • Drug Stability
  • Lethal Dose 50
  • Male
  • Mice
  • Particle Size
  • Particulate Matter / chemistry
  • Particulate Matter / toxicity*
  • Ricin / chemistry
  • Ricin / toxicity*

Substances

  • Aerosols
  • Particulate Matter
  • Ricin