Solid lipid nanoparticles encapsulating a fluorescent marker (coumarin 6) and antimalarials – artemether and lumefantrine: evaluation of cellular uptake and antimalarial activity

Abstract

AbstractArtemisinins, the mainstay in the treatment of malaria today, are used in combination with other antimalarials to forestall resistance, as artemisinin-combination therapies. In line with the World Health Organization’s recommendation in that respect, solid lipid nanoparticles (SLN) were formulated to encapsulate two antimalarial drugs — artemether and lumefantrine. The nanoparticles were evaluated for size and solid state properties. Caco-2 cells were used to investigate the ability of the SLN to deliver its payload at the absorptive interface of the gastrointestinal tract. Mice heart endothelial cells (MHEC) were also used as marker cells to assess cellular uptake of coumarin 6 from the SLN with imaging by confocal laser scanning microscopy (CSLM). In vivo antimalarial activity was done using a standard suppressive protocol. The results of this study revealed different crystal properties for artemether and lumefantrine, which affected their solubility in the lipid matrix and thus, loading in the lipid nanoparticles. The particles of the SLN were within the range of 150 nm–500 nm with varied polydispersity indices. Wide angle X-ray diffraction analysis indicated the presence of particles of solid nature. Cellular uptake studies indicated uptake of coumarin 6 from the coumarin 6-labeled SLN. In vivo antimalarial studies indicated high clearance of parasitemia with minimal effect on hematological parameters tested.