Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria

Abstract Background Malaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential fo...

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Main Authors: Bianca Portugal Tavares de Moraes, Karoline Paiva da Silva, Karina Paese, Adilson Paulo Sinhorin, Silvia S. Guterres, Adriana R. Pohlmann, Isabelle Moraes-de-Souza, Sarah de Oliveira Rodrigues, Kauê Francisco Corrêa e SouzaSouza, Carolina Medina Coeli da Cunha, Matheus Augusto Patrício de Almeida, Patrícia Torres Bozza, Hugo Caire de Castro-Faria-Neto, Adriana Ribeiro Silva, Cassiano Felippe Gonçalves-de-Albuquerque, Stela Regina Ferrarini
Format: Article
Language:English
Published: Springer 2024-11-01
Series:Discover Nano
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Online Access:https://doi.org/10.1186/s11671-024-04121-6
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author Bianca Portugal Tavares de Moraes
Karoline Paiva da Silva
Karina Paese
Adilson Paulo Sinhorin
Silvia S. Guterres
Adriana R. Pohlmann
Isabelle Moraes-de-Souza
Sarah de Oliveira Rodrigues
Kauê Francisco Corrêa e SouzaSouza
Carolina Medina Coeli da Cunha
Matheus Augusto Patrício de Almeida
Patrícia Torres Bozza
Hugo Caire de Castro-Faria-Neto
Adriana Ribeiro Silva
Cassiano Felippe Gonçalves-de-Albuquerque
Stela Regina Ferrarini
author_facet Bianca Portugal Tavares de Moraes
Karoline Paiva da Silva
Karina Paese
Adilson Paulo Sinhorin
Silvia S. Guterres
Adriana R. Pohlmann
Isabelle Moraes-de-Souza
Sarah de Oliveira Rodrigues
Kauê Francisco Corrêa e SouzaSouza
Carolina Medina Coeli da Cunha
Matheus Augusto Patrício de Almeida
Patrícia Torres Bozza
Hugo Caire de Castro-Faria-Neto
Adriana Ribeiro Silva
Cassiano Felippe Gonçalves-de-Albuquerque
Stela Regina Ferrarini
author_sort Bianca Portugal Tavares de Moraes
collection DOAJ
description Abstract Background Malaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential for improving drug bioavailability and potency while reducing adverse effects. Objectives This study aimed to develop lipid-core nanocapsules containing ART and LUM and evaluate their effects in an experimental cerebral malaria model (ECM). Methods The polymeric interfacial deposition method was used to develop lipid-core nanocapsules (LNCs) containing ART and LUM (LNCARTLUM) and were characterized using micrometric and nanometric scales. Male C57BL/6 mice were infected with Plasmodium (P.) berghei ANKA (PbA, 1 × 105 PbA-parasitized red blood cells, intraperitoneally). On day 5 post-infection, PbA-infected mice were orally administered with ART + LUM, LNCARTLUM, blank nanocapsules (LNCBL), or ethanol as a control. Parasitemia, clinical scores, and survival rates were monitored throughout the experiment. Organ-to-body weight ratios, cytokine quantification, and intravital microscopy analyses were conducted on day 7 post-infection. Results LNCs were successfully developed and characterized. The treatment with LNCARTLUM in ECM resulted in complete clearance of parasitemia at 10 dpi, decreased clinical scores, and maintained 100% survival rates. Thereated mice exhibited splenomegaly and reduced TNF-α, IL-1β, and MCP1 levels in the brain. Furthermore, the LNCARTLUM treatment protected the brain microvasculature, reducing the number of cells in the rolling process and adherent to the microvasculature endothelium. Conclusion Nanoformulations can potentially improve the efficacy of antimalarial drugs and be considered a promising approach to treat malaria.
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spelling doaj-art-5c7f21adc90544aea97ee65e9bd68bf52024-11-17T12:43:32ZengSpringerDiscover Nano2731-92292024-11-0119111410.1186/s11671-024-04121-6Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malariaBianca Portugal Tavares de Moraes0Karoline Paiva da Silva1Karina Paese2Adilson Paulo Sinhorin3Silvia S. Guterres4Adriana R. Pohlmann5Isabelle Moraes-de-Souza6Sarah de Oliveira Rodrigues7Kauê Francisco Corrêa e SouzaSouza8Carolina Medina Coeli da Cunha9Matheus Augusto Patrício de Almeida10Patrícia Torres Bozza11Hugo Caire de Castro-Faria-Neto12Adriana Ribeiro Silva13Cassiano Felippe Gonçalves-de-Albuquerque14Stela Regina Ferrarini15Post-Graduation Program in Neuroscience, Fluminense Federal UniversityHealth Sciences Post-Graduation Program, Federal University Mato GrossoEnvironmental SciencesPost-Graduation Program, Federal University of Mato GrossoEnvironmental SciencesPost-Graduation Program, Federal University of Mato GrossoPharmaceutical Sciences Post-Graduation Program, Federal University of Rio Grande Do SulPharmaceutical Sciences Post-Graduation Program, Federal University of Rio Grande Do SulImmunopharmacology Laboratory, Federal University of State of Rio de JaneiroImmunopharmacology Laboratory, Federal University of State of Rio de JaneiroImmunopharmacology Laboratory, Federal University of State of Rio de JaneiroImmunopharmacology Laboratory, Oswaldo Cruz InstitutImmunopharmacology Laboratory, Oswaldo Cruz InstitutImmunopharmacology Laboratory, Oswaldo Cruz InstitutImmunopharmacology Laboratory, Oswaldo Cruz InstitutPost-Graduation Program in Neuroscience, Fluminense Federal UniversityImmunopharmacology Laboratory, Federal University of State of Rio de JaneiroHealth Sciences Post-Graduation Program, Federal University Mato GrossoAbstract Background Malaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential for improving drug bioavailability and potency while reducing adverse effects. Objectives This study aimed to develop lipid-core nanocapsules containing ART and LUM and evaluate their effects in an experimental cerebral malaria model (ECM). Methods The polymeric interfacial deposition method was used to develop lipid-core nanocapsules (LNCs) containing ART and LUM (LNCARTLUM) and were characterized using micrometric and nanometric scales. Male C57BL/6 mice were infected with Plasmodium (P.) berghei ANKA (PbA, 1 × 105 PbA-parasitized red blood cells, intraperitoneally). On day 5 post-infection, PbA-infected mice were orally administered with ART + LUM, LNCARTLUM, blank nanocapsules (LNCBL), or ethanol as a control. Parasitemia, clinical scores, and survival rates were monitored throughout the experiment. Organ-to-body weight ratios, cytokine quantification, and intravital microscopy analyses were conducted on day 7 post-infection. Results LNCs were successfully developed and characterized. The treatment with LNCARTLUM in ECM resulted in complete clearance of parasitemia at 10 dpi, decreased clinical scores, and maintained 100% survival rates. Thereated mice exhibited splenomegaly and reduced TNF-α, IL-1β, and MCP1 levels in the brain. Furthermore, the LNCARTLUM treatment protected the brain microvasculature, reducing the number of cells in the rolling process and adherent to the microvasculature endothelium. Conclusion Nanoformulations can potentially improve the efficacy of antimalarial drugs and be considered a promising approach to treat malaria.https://doi.org/10.1186/s11671-024-04121-6Lipid core nanocapsulesCerebral malariaLumefantrineArtemetherMicrocirculation
spellingShingle Bianca Portugal Tavares de Moraes
Karoline Paiva da Silva
Karina Paese
Adilson Paulo Sinhorin
Silvia S. Guterres
Adriana R. Pohlmann
Isabelle Moraes-de-Souza
Sarah de Oliveira Rodrigues
Kauê Francisco Corrêa e SouzaSouza
Carolina Medina Coeli da Cunha
Matheus Augusto Patrício de Almeida
Patrícia Torres Bozza
Hugo Caire de Castro-Faria-Neto
Adriana Ribeiro Silva
Cassiano Felippe Gonçalves-de-Albuquerque
Stela Regina Ferrarini
Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
Discover Nano
Lipid core nanocapsules
Cerebral malaria
Lumefantrine
Artemether
Microcirculation
title Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
title_full Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
title_fullStr Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
title_full_unstemmed Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
title_short Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
title_sort effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria
topic Lipid core nanocapsules
Cerebral malaria
Lumefantrine
Artemether
Microcirculation
url https://doi.org/10.1186/s11671-024-04121-6
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