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

Souza, Ana Carolina Moreira; Mosqueira, Vanessa Carla Furtado; Silveira, Ana Paula Amariz; Antunes, Lidiane Rodrigues; Richard, Sylvain; Guimarães, Homero Nogueira; Grabe‐Guimarães, Andrea

doi:10.1017/s0031182017002207

Cited by 16 publications

(28 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They can encapsulate different lipophilic molecules at high payloads and are biodegradable. They have demonstrated outstanding potential to reduce the cardiotoxicity of several drug candidates such as artemether, halofantrine, and lychnopholide, as reported by our group [ 17 , 18 , 19 , 20 ]. These properties may reflect NC’s ability to control drug release in the blood, reducing the free fraction producing potentially toxic adverse effects.…”

Section: Introductionmentioning

confidence: 82%

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

et al. 2021

Self Cite

View full text Add to dashboard Cite

Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,β/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5–450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. We administered intravenously Lyso-7, Lyso-7-NC, control, and blank-NC once a day for seven days in mice. We assessed cell contraction and intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. Lyso-7 reduced cell contraction and accelerated relaxation while lowering diastolic Ca2+ and reducing Ca2+ transient amplitude. Lyso-7 also promoted abnormal ectopic diastolic Ca2+ events, which isoproterenol dramatically enhanced. Incorporation of Lyso-7 in NC attenuated drug effects on cell contraction and prevented its impact on relaxation, diastolic Ca2+, Ca2+ transient amplitude, Ca2+ transient decay kinetics, and promotion of diastolic Ca2+ events. Acute effects of Lyso-7 on cardiomyocytes in vitro at high concentrations (450 nM) were globally similar to those observed after repeated administration in vivo. In conclusion, we show evidence for off-target effects of Lyso-7, seen during acute exposure of cardiomyocytes to high concentrations and after repeated treatment in mice. Nano-encapsulation of Lyso-7 in polymeric NC attenuated the unwanted effects, particularly ectopic Ca2+ events known to support life-threatening arrhythmias favored by stress or exercise.

show abstract

Section: Introductionmentioning

confidence: 82%

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Artemether is an effective drug for reducing parasitaemia in malaria and increasing the survival of mice infected with P. berghei (Souza et al, 2018). Remarkably, effectiveness of artemether and other antimalarial drugs can be improved by nanoencapsulation that prolongs their effect (Haas, Bettoni, de Oliveira, Guterres, & Dalla Costa, 2009;Leite et al, 2007;Mosqueira et al, 2004;Souza et al, 2018). F I G U R E 7 Nanoencapsulation prevents the occurrence of irregular Ca 2+ transients during pacing and spontaneous diastolic Ca 2+ events in single left ventricular myocytes following repeated-dose treatment of mice with artemether.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation

Souza

Grabe‐Guimarães

Cruz

et al. 2020

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and Purpose The artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC‐ATM) is more efficient than free artemether for reducing parasitaemia and increasing survival of Plasmodium berghei‐infected mice. NCs also prevent prolongation of the QT interval of the ECG. Here, we assessed cellular cardiotoxicity of artemether and how this toxicity was prevented by nanoencapsulation. Experimental Approach Mice were treated with NC‐ATM orally (120 mg·kg−1 twice daily) for 4 days. Other mice received free artemether, blank NCs, and vehicle for comparison. We measured single‐cell contraction, intracellular Ca2+ transient using fluorescent Indo‐1AM Ca2+ dye, and electrical activity using the patch‐clamp technique in freshly isolated left ventricular myocytes. The acute effect of free artemether was also tested on cardiomyocytes of untreated animals. Key Results Artemether prolonged action potentials (AP) upon acute exposure (at 0.1, 1, and 10 μM) of cardiomyocytes from untreated mice or after in vivo treatment. This prolongation was unrelated to blockade of K+ currents, increased Ca2+ currents or promotion of a sustained Na+ current. AP lengthening was abolished by the NCX inhibitor SEA‐0400. Artemether promoted irregular Ca2+ transients during pacing and spontaneous Ca2+ events during resting periods. NC‐ATM prevented all effects. Blank NCs had no effects compared with vehicle. Conclusion and Implications Artemether induced NCX‐dependent AP lengthening (explaining QTc prolongation) and disrupted Ca2+ handling, both effects increasing pro‐arrhythmogenic risks. NCs prevented these adverse effects, providing a safe alternative to the use of artemether alone, especially to treat malaria.

show abstract

“… Healthy BALB/c mice Parasite infection treatment (malaria) – Polysorbate 80 nanocarriers or Eudragit ® RS100 nanocarriers 174 , 175 Quinine; curcumin i.p. Wild-type N2 Bristol strain of Caenorhabditis elegans; Plasmodium berghei-infected Swiss mice Parasite infection treatment (malaria) – PCL nanocarriers 176 Artemether Orally Healthy and Plasmodium berghei-infected C57BL/6 mice Parasite infection treatment (malaria) – Abbreviations: i.g., intragastric; i.p., intraperitoneal; i.v., intravenous; PCL, poly-e-caprolactone; PEG, poly(ethylene glycol); PLGA, poly(lactide-co-glycolide). …”

Section: Other Diseasesmentioning

confidence: 99%

<p>Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature</p>

Karabasz¹,

Bzowska²,

Szczepanowicz³

2020

IJN

View full text Add to dashboard Cite

Polymeric nanomaterials have become a prominent area of research in the field of drug delivery. Their application in nanomedicine can improve bioavailability, pharmacokinetics, and, therefore, the effectiveness of various therapeutics or contrast agents. There are many studies for developing new polymeric nanocarriers; however, their clinical application is somewhat limited. In this review, we present new complex and multifunctional polymeric nanocarriers as promising and innovative diagnostic or therapeutic systems. Their multifunctionality, resulting from the unique chemical and biological properties of the polymers used, ensures better delivery, and a controlled, sequential release of many different therapeutics to the diseased tissue. We present a brief introduction of the classical formulation techniques and describe examples of multifunctional nanocarriers, whose biological assessment has been carried out at least in vitro. Most of them, however, also underwent evaluation in vivo on animal models. Selected polymeric nanocarriers were grouped depending on their medical application: anti-cancer drug nanocarriers, nanomaterials delivering compounds for cancer immunotherapy or regenerative medicine, components of vaccines nanomaterials used for topical application, and lifestyle diseases, ie, diabetes.

show abstract

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

Cited by 16 publications

References 46 publications

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation

<p>Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature</p>

Contact Info

Product

Resources

About