Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 14;19(1):184.
doi: 10.1186/s11671-024-04121-6.

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

Bianca Portugal Tavares de Moraes #  1   2   3 , Karoline Paiva da Silva #  4 , Karina Paese  5 , Adilson Paulo Sinhorin  5 , Silvia S Guterres  6 , Adriana R Pohlmann  6 , Isabelle Moraes-de-Souza  2 , Sarah de Oliveira Rodrigues  2 , Kauê Francisco Corrêa E SouzaSouza  2 , Carolina Medina Coeli da Cunha  3 , Matheus Augusto Patrício de Almeida  3 , Patrícia Torres Bozza  3 , Hugo Caire de Castro-Faria-Neto  3 , Adriana Ribeiro Silva  1   3 , Cassiano Felippe Gonçalves-de-Albuquerque #  7   8 , Stela Regina Ferrarini #  9
Affiliations

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

Bianca Portugal Tavares de Moraes et al. Discov Nano. .

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.

Keywords: Artemether; Cerebral malaria; Lipid core nanocapsules; Lumefantrine; Microcirculation.

PubMed Disclaimer

Conflict of interest statement

Declarations Competing interests The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Light intensity captured by the camera over 60 s as a function of the particle diameter, based on the particle movement tracking technique (NanoSight®), for formulations and photomicrography of LNCARTLUM.. A LNCARTLUM, B LNCBL. In detail, the particle diameter distribution by relative intensity is demonstrated. C Photomicrography of LNCARTLUM
Fig. 2
Fig. 2
In vitro release profile of non-nanoencapsulated lumefantrine (LUM) and lipid-core nanocapsules (LNCs) containing artemether and lumefantrine (LNCARTLUM)
Fig. 3
Fig. 3
Schematic representation of experimental design. A Mice were infected with PbA and divided into 4 groups: ART + LUM, ethanol, LNCBL, and LNCARTLUM. B Parasitemia, Clinical Score, and survival were assessed on 5–14 dpi. The organ weight, cerebral cytokines levels, and microcirculation analysis were evaluated on 7 dpi
Fig. 4
Fig. 4
The survival rate of C57Bl-6 mice infected with PbA and treated with LNCARTLUM and ART + LUM. Post-infection, mice were followed daily for 14 days. LNCARTLUM treatment had a survival of 100% mice compared to non-infected mice, whereas ART + LUM had a 60% survival rate. Analysis was performed using the Kaplan–Mayer curve followed by the Mantel–Cox test *p < 0.05; **p < 0.005 (n = 10)
Fig. 5
Fig. 5
Evaluation of ART + LUM and LNCARTLUM on the experimental CM model. A. Parasitemia in mice at 5, 7, 10, and 14 dpi (n = 10–20). * LNCBL compared with LNCARTLUM and # LNCARTLUM compared with ART + LUM. #p < 0.01, **p < 0.006, ***p < 0.0003. B. Clinical Score in mice at 7, 10, and 14 dpi. *p < 0.05; ***p < 0.001, ****p < 0.0001. C. Linear regression analysis between the clinical scores of LNCARTLUM mice at 7 dpi and parasitemia. D. Linear regression analysis between clinical score of LNCBL and parasitemia. Data are presented as means ± standard deviations
Fig. 6
Fig. 6
Evaluation of ART + LUM and LNCARTLUM on the experimental CM mode. Spleen and liver indices were measured relative to the body weight on 7 dpi. A. Liver/ body weight ratio. **p < 0.008. B. Spleen/ body weight ratio. *p < 0.05, **p < 0.001, ***p < 0.0003(n = 4–11)
Fig. 7
Fig. 7
LNCARTLUM treatment results in decreased inflammatory markers in the brain tissue. Cytokines were measured by ELISA. A TNF-α, B IL-6, C IL-1β, D MCP-1, E KC. *p < 0.01, **p < 0.001, ***p < 0.0005, ****p < 0.0001(n = 5–8)
Fig. 8
Fig. 8
LNCARTLUM treatment increased rolling velocity and severely impaired neutrophil adhesion in the brain microvasculature of PbA-infected mice on 7 dpi. Brain intravital microscopy was performed to assess leukocyte rolling and adhesion to the wall’s vasculature. A Representative images of brain microcirculation of NI and PbA-infected mice treated with LNCBL, ART + LUM and LNCARTLUM under intravital microscopy. B The number of rolling cells/min. C Adherent cells were assessed over 1 min of observation. *p < 0.02, **p < 0.003, ***p < 0.0005, ****p < 0.0001
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Varo R, Chaccour C, Bassat Q. Update on malaria. Med Clin (Barc). 2020;155(9):395–402. - PubMed
    1. WHO, W.H.O., World malaria report 2023, L.C.B.-N.-S. IGO., Editor. 2023, World Health Organization: Geneva.
    1. Poespoprodjo JR, et al. Malaria. Lancet. 2023;402(10419):2328–45. - PubMed
    1. Hadjilaou A, et al. Pathogenetic mechanisms and treatment targets in cerebral malaria. Nat Rev Neurol. 2023;19(11):688–709. - PubMed
    1. Wassmer SC, et al. Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis. Trends Parasitol. 2024;40(1):28–44. - PMC - PubMed

LinkOut - more resources