Discover nano · 2024
Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria.
СтатьяНазвание и аннотация: Перевод в очереди
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de Moraes Bianca Portugal Tavares, da Silva Karoline Paiva, Paese Karina, Sinhorin Adilson Paulo, Guterres Silvia S, Pohlmann Adriana R, Moraes-de-Souza Isabelle, de Oliveira Rodrigues Sarah, SouzaSouza Kauê Francisco Corrêa E, da Cunha Carolina Medina Coeli, de Almeida Matheus Augusto Patrício, Bozza Patrícia Torres, de Castro-Faria-Neto Hugo Caire, Silva Adriana Ribeiro, Gonçalves-de-Albuquerque Cassiano Felippe, Ferrarini Stela Regina
Аннотация
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.
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.