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

Published online by Cambridge University Press:  10 December 2017

Ana Carolina Moreira Souza ,
Vanessa Carla Furtado Mosqueira ,
Ana Paula Amariz Silveira ,
Lidiane Rodrigues Antunes ,
Sylvain Richard ,
Homero Nogueira Guimarães  and
Andrea Grabe-Guimarães Open the ORCID record for Andrea Grabe-Guimarães [Opens in a new window]
Ana Carolina Moreira Souza
Affiliation:
Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
Vanessa Carla Furtado Mosqueira
Affiliation:
Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
Ana Paula Amariz Silveira
Affiliation:
Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
Lidiane Rodrigues Antunes
Affiliation:
Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
Sylvain Richard
Affiliation:
Physiologie et Médecine Expérimentale du Cœur et des Muscles–PHYMEDEXP, Univ Montpellier, CNRS UMR 9214, INSERM U1046, Montpellier, France
Homero Nogueira Guimarães
Affiliation:
Department of Electrical Engineering, Federal University of Minas Gerais, Belo Horizonte, Brazil
Andrea Grabe-Guimarães*
Affiliation:
Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
*
Author for correspondence: Andrea Grabe-Guimarães, E-mail: [email protected], [email protected]
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Abstract

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

Artemethercardiotoxicityelectrocardiogrammalariapolymeric nanocapsulesQT interval
Type
Research Article
Information
Parasitology , Volume 145 , Issue 8 , July 2018 , pp. 1075 - 1083
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Copyright
Copyright © Cambridge University Press 2017 

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