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

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 (LNC_ARTLUM) 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, LNC_ARTLUM, blank nanocapsules (LNC_BL), 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 LNC_ARTLUM 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 LNC_ARTLUM 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.