Reduced cardiotoxicity and increased oral efficacy of artemether polymeric nanocapsules in Plasmodium berghei-infected mice

Parasitology. 2018 Jul;145(8):1075-1083. doi: 10.1017/S0031182017002207. Epub 2017 Dec 10.


Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at doses 40, 80 or 120 mg kg-1. Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATM-NC (120 mg kg-1) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.

Keywords: Artemether; QT interval; cardiotoxicity; electrocardiogram; malaria; polymeric nanocapsules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antimalarials / administration & dosage*
  • Antimalarials / toxicity
  • Artemether / administration & dosage*
  • Artemether / toxicity
  • Cardiotoxicity / prevention & control*
  • Disease Models, Animal
  • Electrocardiography
  • Female
  • Malaria / drug therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanocapsules / chemistry*
  • Plasmodium berghei / drug effects*


  • Antimalarials
  • Nanocapsules
  • Artemether