Botulinum Toxin-Chitosan Nanoparticles Prevent Arrhythmia in Experimental Rat Models

Mar Drugs. 2020 Aug 2;18(8):410. doi: 10.3390/md18080410.

Abstract

Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation and rapid atrial pacing models. The present study examined the antiarrhythmic effect of specially formulated BoNT/A1-chitosan nanoparticles (BTN) in calcium chloride-, barium chloride- and electrically induced arrhythmia rat models. BTN enhanced the effect of BoNT/A1. Subepicardial injection of BTN resulted in a significant antiarrhythmic effect in investigated rat models. BTN formulation antagonizes arrhythmia induced by the activation of Ca, K and Na channels.

Keywords: antiarrhythmics; botulinum toxin A1; chitosan nanoparticles; electrically induced arrhythmia; pharmacological models of arrhythmia.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Anti-Arrhythmia Agents / chemistry
  • Anti-Arrhythmia Agents / pharmacology*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control*
  • Botulinum Toxins, Type A / chemistry
  • Botulinum Toxins, Type A / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Chitosan / chemistry
  • Disease Models, Animal
  • Drug Compounding
  • Heart Conduction System / drug effects*
  • Heart Conduction System / metabolism
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects*
  • Male
  • Nanoparticles*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Rats, Wistar
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism

Substances

  • Anti-Arrhythmia Agents
  • Calcium Channels
  • Potassium Channels
  • Sodium Channels
  • Chitosan
  • Botulinum Toxins, Type A
  • incobotulinumtoxinA