Botulinum toxin A: is it really that fragile a molecule?

Abstract

Background: Botulinum toxin A is considered to be an extremely fragile molecule, with recommended usage of some reconstituted botulinum toxin A formulations within 4 hours of reconstitution. Extreme caution is recommended to avoid agitation of the vial.

Objective: To determine whether the effect of reconstituted botulinum toxin A is maintained even when it is agitated vigorously.

Design: Experimental, comparative, animal study.

Participants: Sixty-four white Swiss Webster mice, aged 2 to 4 weeks, arranged in eight separate groups.

Intervention: Reconstituted onabotulinumtoxinA (2.5 U/0.1 mL) was placed securely in a battery-operated mechanized apparatus. The apparatus with the vial was placed in the refrigerator, and the apparatus continuously inverted and straightened the onabotulinumtoxinA vial 30 times a minute. Eight mice were each injected intraperitoneally with 1 U of the agitated onabotulinumtoxinA on days 1, 3, 5, 7, 14, 21, 28, and 42, to evaluate the efficacy of the continuously agitated onabotulinumtoxinA.

Main outcome measure: Death of the mice, demonstrating efficacy of the onabotulinumtoxinA molecule.

Results: Half of each group of mice (4/8 mice) died within 48 hours of the injection (range 16-48 hours).

Conclusion: The effect of botulinum toxin type A is maintained even when it is agitated vigorously for up to 6 weeks. The authors have indicated no significant interest with commercial supporters.