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

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

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Pharmaceutical Science Program (CiPharma),School of Pharmacy,Federal University of Ouro Preto,Ouro Preto,Minas Gerais,Brazil.
Physiologie et Médecine Expérimentale du Cœur et des Muscles-PHYMEDEXP,Univ Montpellier,CNRS UMR 9214,INSERM U1046,Montpellier,France.
Department of Electrical Engineering,Federal University of Minas Gerais,Belo Horizonte,Brazil.


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.


Artemether; QT interval; cardiotoxicity; electrocardiogram; malaria; polymeric nanocapsules

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