Title: Impact of molecular weight and serotype on botulinum neurotoxin oral toxicity and stability in simulated gastrointestinal tract conditions

Authors: J. Adam Crawford; Jennifer Kronenberg; Jennifer Beare; Rebekah Starner; Angelo Scorpio; Sherry Blight

Addresses: Applied Biology and Aerosol Technology, Battelle Memorial Institute, 505 King Ave., Columbus, Ohio, 43201-4696, USA. ' Atlanta Analytical Services, Battelle Memorial Institute, 1600 Clifton Rd NE, M/S G-18, Atlanta, GA, 30329-4018, USA. ' Applied Biology and Aerosol Technology, Battelle Memorial Institute, 505 King Ave., Columbus, Ohio, 43201-4696, USA. ' Battelle Biomedical Research Center, Battelle Memorial Institute, 1425 Plain City – Georgesville Route 142, West Jefferson, OH 43162-9647, USA. ' National Biodefense Analysis and Countermeasures Center (NBACC), 8300 Research Plaza, Fort Detrick, MD 21702-9211, USA. ' Applied Biology and Aerosol Technology, Battelle Memorial Institute, 505 King Ave., Columbus, Ohio, 43201-4696, USA

Abstract: The botulinum neurotoxins (BoNTs) are among the most lethal substances known to humankind. The work described herein examined the oral toxicity of the BoNTs and compared oral toxicity to in vitro stability in simulated gastrointestinal tract conditions. Our results demonstrate that a majority of the BoNTs tested were less stable in simulated intestinal fluid (SIF) as compared to simulated gastric fluid (SGF), and that oral toxicity correlated with the molecular weight of the BoNT complex. These results suggest that stability in the intestinal tract plays a critical role in the oral toxicity of the BoNTs.

Keywords: botulinum neurotoxins; BoNTs; botulism; simulation; gastric fluids; intestinal fluids; molecular weight; oral toxicity; serotype; stability; gastrointestinal tract.

DOI: 10.1504/TBJ.2012.050193

The Botulinum Journal, 2012 Vol.2 No.2, pp.109 - 118

Published online: 30 Oct 2014 *