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

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. This study aimed to develop lipid-core nanocapsules containing ART and LUM and evaluate their effects in an experimental cerebral malaria model (ECM). 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 × 10 5 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. 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. Nanoformulations can potentially improve the efficacy of antimalarial drugs and be considered a promising approach to treat malaria.