Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-16T14:24:00.307Z Has data issue: false hasContentIssue false
  • English
  • Français

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: agguimar@gmail.com, grabe@ef.ufop.br
Get access Rights & Permissions [Opens in a new window]

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
Check for updates
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aditya, NP, Patankar, S, Madhusudhan, B, Murthy, RSR and Souto, EB (2010) Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration, pharmacokinetics, toxicological and in vivo anti-malarial activity. European Journal of Pharmaceutical Sciences 40, 448–455.Google Scholar
Attili-Qadri, S, Karra, N, Nemirovski, A, Schwob, O, Talmon, Y, Nassar, T and Benita, S (2013) Oral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorption. Proceedings of the National Academy of Sciences of the United State of America 110(43), 17498–17503.Google Scholar
Bassareo, PP and Mercuro, G (2013) QRS complex enlargement as a predictor of ventricular arrhythmias in patients affected by surgically treated tetralogy of Fallot: a comprehensive literature review and historical overview. ISRN Cardiology, 2013, 782508.Google Scholar
Beckman, DA, Youreneff, M and Butt, MT (2013) Neurotoxicity assessment of artemether in juvenile rats. Birth Defects Research Part B – Developmental and Reproductive Toxicology 98, 183–199.Google Scholar
Borsini, F, Crumb, W, Pace, S, Ubben, D, Wible, B, Yan, GX and Funck-Brentano, C (2012) In vitro cardiovascular effects of dihydroartemisin–piperaquine combination compared with other antimalarials. Antimicrobial Agents Chemotherapy 56, 3261–3270.Google Scholar
Branquinho, RT, Pound-Lana, G, Marques, MM, Saúde-Guimarães, DA, Vilela, JMC, Spangler, AM, de Lana, M and Mosqueira, VCF (2017a) Increased body exposure to new anti-trypanosomal through nanoencapsulation. Scientific Reports 7, 1–12a.Google Scholar
Branquinho, RT, Roy, J, Farah, C, Garcia, GM, Aimond, F, Le Guennec, JY, Saude-Guimarães, DA, Grabe-Guimaraes, A, Mosqueira, VCF, Lana, M and Richard, S (2017b) Biodegradable polymeric nanocapsules prevent cardiotoxicity of anti-trypanosomal Lychnopholide. Scientific Reports 7, 44998b.CrossRefGoogle ScholarPubMed
Brossi, A, Venugopalan, B, Dominguez-Gerpe, L, Yeh, HJC, Flippen-Anderson, JL, Buchs, P, Luo, XD, Milhous, W and Peters, W (1988) Arteether, a new antimalarial drug, synthesis and antimalarial properties. Journal of Medicinal Chemistry 31, 645–650.Google Scholar
Chimanuka, B, Gabriëls, M, Detaevernier, MR and Plaizier-Vercammen, JA (2002) Preparation of artemether liposomes, their HPLC–UV evaluation and relevance for clearing recrudescent parasitaemia in Plasmodium chabaudi malaria-infected mice. Journal of Pharmaceutical and Biomedical Analysis 28(1), 13–22.Google Scholar
Classen, W, Altmann, B, Gretener, P, Souppart, C, Skelton-Stroud, P and Krinke, G (1999) Differential effects of orally versus parenterally administered qinghaosu derivative artemether in dogs. Experimental and Toxicologic Pathology 51, 507–516.Google Scholar
Costenaro, P, Benedetti, P, Facchin, C, Mengoli, C and Pellizzer, G (2011) Fatal myocarditis in course of Plasmodium falciparum infection, case report and review of cardiac complications in malaria. Case Reports in Medicine 2011, 1–5.Google Scholar
Crumb, W and Cavero, I (1999) QT interval prolongation by non-cardiovascular drugs, issues and solutions for novel drug development. Pharmaceutical Science and Technology 2, 270–280.Google Scholar
De Mello, CGC, Branquinho, RT, Oliveira, MT, Milagre, MM, Saúde-Guimarães, DA, Mosqueira, VCF and Lana, M (2016) Efficacy of Lychnopholide polymeric nanocapsules after oral and intravenous administration in murine experimental Chagas disease. Antimicrobial Agents and Chemotherapy 60, 5215–5222.CrossRefGoogle ScholarPubMed
Efferth, T and Kaina, B (2010) Toxicity of the antimalarial artemisinine and its derivatives. Critical Reviews in Toxicology 40(5), 405–421.Google Scholar
Farraj, AK, Hazari, MS and Cascio, WE (2011) The utility of the small rodent electrocardiogram in toxicology. Toxicological Sciences 121(1), 11–30.Google Scholar
Fermini, B and Fossa, AA (2003) The impact of drug-induced qt interval prolongation on drug discovery and development. Nature Reviews. Drug Discovery 2, 439–447.Google Scholar
Fessi, H, Puisieux, F, Devissaguet, JP, Ammoury, N and Benita, S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics 55, 1–4.Google Scholar
Galindo-Rodriguez, SA, Allemann, E, Fessi, H and Doelker, E (2005) Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Critical Reviews in Therapeutic Drug Carrier Systems 22, 419–463.CrossRefGoogle ScholarPubMed
Holmqvist, F, Thomas, KL, Broderick, S, Ersbøll, M, Singh, D, Chiswell, K, Shaw, LK, Hegland, DD, Velazquez, EJ and Daubert, JP (2015) Clinical outcome as a function of the PR-interval- there is virtue in moderation, data from the duke databank for cardiovascular disease. Europace 17, 978–985.Google Scholar
Idro, R, Jenkins, NE and Newton, CR (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurology 4, 827–840.Google Scholar
Jain, A, Kaushik, R and Kaushik, RM (2016) Malarial hepatopathy, clinical profile and association with other malarial complications. Acta Tropica 159, 95–105.Google Scholar
Karbwang, J, Na-Bangchang, K, Congpuong, K, Molunto, P and Thanavibul, A (1997) Pharmacokinetics and bioavailability of oral and intramuscular artemether. European Journal of Clinical Pharmacology 52(4), 307–310.Google Scholar
Khoury, DS, Cromer, D, Elliott, T, Soon, MSF, Thomas, BS, James, KR, Best, SE, Aogo, RA, Engel, JA, Gartlan, KH, Akter, J, Sebina, I, Haque, A and Davenport, MP (2017) Characterizing the effect of antimalarial drugs on the maturation and clearance of murine blood-stage Plasmodium parasites in vivo. International Journal for Parasitology 47, 913–922.Google Scholar
Laxmi, M, Bhardwaj, A, Mehta, S and Mehta, A (2015) Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artificial Cells, Nanomedicine, and Biotechnology 43(5), 334–344.Google Scholar
Legrand, P, Barratt, G, Mosqueira, V, Fessi, H and Devissaguet, JP (1999) Polymeric nanocapsules as drug delivery systems – a review. STP Pharma Sciences 9, 411–418.Google Scholar
Leite, EA, Grabe-Guimarães, A, Guimarães, HN, Machado-Coelho, GLL, Barratt, G and Mosqueira, VCF (2007) Cardiotoxicity reduction induced by halofantrine entrapped in nanocapsule devices. Life Sciences 80, 1327–1334.Google Scholar
Looareesuwan, S, White, N, Chanthavanich, P, Edwards, G, Nicholl, D, Bunch, C and Warrell, DA (1986) Cardiovascular toxicity and distribution kinetics of intravenous chloroquine. British Journal Clinical Pharmacology 22, 31–36.Google Scholar
Maguire, GP, Handojo, T, Pain, MCF, Kenangalem, E, Ric, N, Tjitra, E and Anstey, NM (2008) Lung injury in uncomplicated and severe Falciparum malaria, a longitudinal study in Papua, Indonesia. The Journal of Infectious Diseases 192, 1966–1974.Google Scholar
Mandawgadea, SD, Sharma, S, Pathak, S and Patravale, VB (2008) Development of SMEDDS using natural lipophile, application to -artemether delivery. International Journal of Pharmaceutics 362, 179–183.Google Scholar
Manning, J, Vanachayangkul, P, Lon, C, Spring, M, So, M, Sea, D, Se, Y, Somethy, S, Phann, ST, Chann, S, Sriwichai, S, Buathong, N, Kuntawunginn, W, Mitprasat, M, Siripokasupkul, R, Teja-Isavadharm, P, Soh, E, Timmermans, A, Lanteri, C, Kaewkungwal, J, Auayporn, M, Tang, D, Chour, CM, Prom, S, Haigney, M, Cantilena, L and Saunders, D (2014) Randomized, double-blind, placebo-controlled clinical trial of a two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted for concern over prolonged corrected QT interval. Antimicrobial Agents Chemotherapy 58, 6056–6067.Google Scholar
McClean, S, Prosser, E, Meehan, E, O'Malley, D, Clarke, N, Ramtoola, Z and Brayden, D (1998) Binding and uptake of biodegradable poly-DL-lactide micro- and nanoparticles in intestinal epithelia. European Journal of Pharmaceutical Sciences 6(2), 153–163.Google Scholar
Mecca, TE, Elam, J, Nash, CB and Caldwell, RW (1980) α-Adrenergic blocking properties of quinine HCI 1. European Journal Pharmacology 63, 159–166.Google Scholar
Mohsen, AH, Green, ST, McKendrick, MW and West, JN (2001) Myocarditis associated with Plasmodium falciparum malaria, a case report and a review of the literature. Journal Travel Medicine 8, 219–220.Google Scholar
Mosqueira, VCF, Loiseau, PM, Bories, C, Legrand, P, Devissaguet, JP and Barratt, G (2004) Efficacy and pharmacokinetics of intravenous nanocapsule formulations of halofantrine in Plasmodium berghei-infected mice. Antimicrobial Agents and Chemotherapy 48(4), 1222–1228.Google Scholar
Ngouesse, B, Basco, LK, Ringwald, P, Keundjian, A and Blackett, KN (2001) Cardiac effects of amodiaquine and sulfadoxine-pyrimethamine in malaria-infected African patients. The American Journal of Tropical Medicine and Hygiene 65, 711–716.Google Scholar
Patten, RD (2007) Models of gender differences in cardiovascular disease. Drug Discovery Today, Disease Models 4(4), 227–232.Google Scholar
Peters, W, Ze-Lin, L, Robinson, B and Warhurst, DC (1986) The chemoterapy of rodent malaria. Annals of Tropical Medicine and Parasitology 80, 483–489.Google Scholar
Plewes, K, Kingston, HWF, Ghose, A, Maude, RJ, Herdman, MT, Leopold, SJ, Ishioka, H, Hasan, MMU, Haider, MS, Alam, S, Piera, KA, Charunwatthana, P, Silamut, K, Yeo, TW, Faiz, MA, Lee, SJ, Mukaka, M, Turner, GDH, Anstey, NM, Roberts, LJ, White, NJ, Day, NPJ, Hossain, A and Dondorp, AM (2017) Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria, an observational study. BMC Infectious Diseases 17, 313–325.Google Scholar
Prabhu, P, Suryavanshi, S, Pathak, S, Sharma, S and Patravale, V (2016) Artemether–lumefantrine nanostructured lipid carriers for oral malaria therapy, enhanced efficacy at reduced dose and dosing frequency. International Journal Pharmaceutics 511, 473–487.Google Scholar
Redfern, WS, Carlsson, L, Davis, AS, Lynch, WG, MacKenzie, I, Palethorpe, S, Siegl, PK, Strang, I, Sullivan, AT, Wallis, R, Camm, AJ and Hammond, TG (2003) Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs, evidence for a provisional safety margin in drug development. Cardiovascular Research 58, 32–45.Google Scholar
Sadoh, WE and Uduebor, JO (2016) Electrocardiographic changes and troponin T levels in children with severe malaria anemia and heart failure. Nigerian Journal of Clinical Practice 20(5), 556–559.Google Scholar
Salvi, V, Karnad, DR, Panicker, GK and Kothari, S (2010) Update on the evaluation of a new drug for effects on cardiac repolarization in humans, issues in early drug development. British Journal Pharmacology 159, 34–48.Google Scholar
Silamut, K, Newton, PN, Teja-Isavadharm, P, Suputtamongkol, Y, Siriyanonda, D, Rasameesoraj, M, Pukrittayakamee, S and White, NJ (2003) Artemether bioavailability after oral or intramuscular administration in uncomplicated Falciparum malaria. Antimicrobial Agents Chemotherapy 47, 3795–3798.CrossRefGoogle ScholarPubMed
Stoute, JA, Odindo, AO, Owuor, BO, Mibei, EK, Opollo, MO and Waitumbi, JN (2003) Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. Journal Infectious Diseases 187, 522–525.Google Scholar
Surawicz, B, Childers, R, Deal, BJ, Gettes, LS, Bailey, JJ and Gorgels, A (2007) Recommendations for the standardization and interpretation of the electrocardiogram. Journal of the American College of Cardiology 49, 1109–1127.Google Scholar
Torre-Amione, G, Kapadia, S, Benedict, C, Oral, H, Young, JB and Mann, DL (1996) Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction, a report from the studies of left ventricular dysfunction (SOLVD). Journal of the American College of Cardiology 27, 1201–1206.Google Scholar
Tripathy, S, Das, S, Chakraborty, SP, Sahu, SK, Pramanik, P and Roy, S (2012) Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: A dose and duration dependent approach. International Journal of Pharmaceutics 434, 292–305.Google Scholar
Vidal-Diniz, AT. (2014) Artemeter nanocapsules of, physical-chemical characterization, cardiotoxicity, neurotoxicity and efficacy in experimental malaria. PhD theses, Federal University of Ouro Preto, Ouro Preto, Brazil.Google Scholar
World Health Organization (2016a) Artemisinin and artemisinin-based combination therapy resistance, status report. Available at http//www.who.int/iris/handle/10665/208820. (Accessed 2 September 2017).Google Scholar
World Health Organization (2016b). Summary. Geneva, World Malaria Report; (2017) (WHO/HTM/GMP/2017.4). Licence, CC BY-NC-SA3.0 IGO. Available at http//apps.who.int/iris. (Accessed 27 August 2017).Google Scholar
Yin, JY, Wang, HM, Wang, QJ, Dong, YS, Han, G, Guan, YB, Zhao, KY, Qu, WS, Yuan, Y, Gao, XX, Jing, SF and Ding, RG (2014) Subchronic toxicological study of two artemisinine derivatives in dogs. PLoS ONE 9(4), e94034.Google Scholar