doi:10.1038/nindia.2014.94 Published online 16 July 2014
Researchers have synthesized nanosized lipid
drug carriers that can efficiently deliver two different combinations of
antimalarial drugs to red blood cells infected by malaria parasites1. These
drug-carrying lipids could potentially be used to deliver antimalarial drugs
for treating malignant malaria.
Studies have shown that malaria parasites are developing increasing resistance to most antimalarial drugs. In addition, high doses of antimalarial drugs are detrimental to human health. To address these problems of toxicity and resistance, the researchers synthesized the nanolipid drug carriers from glyceryl dilaurate.
They infected mice with Plasmodium berghei, which causes malaria in mice, and then cultured their red blood cells. They also cultured human red blood cells infected with Plasmodium falciparum, which causes malignant malaria in humans. They then used these infected red blood cells and the parasite-infected mice to test the efficacy of the drug carriers in delivering two different combinations of antimalarial drugs: artemether with clindamycin and artemether with lumefantrine.
The researchers found that the drug carriers loaded with artemether and lumefantrine at 5% of the standard oral dose of this combination protected the mice against the parasites even after 45 days. The drug carriers loaded with artemether and clindamycin at lower doses than their oral therapeutic doses also protected the mice against the parasites.
The researchers claim that the drug-loaded nanolipid carriers entered the mitochondria of the infected red blood cells, where they probably generated reactive oxygen species. These oxygen species caused the infected red blood cells to rupture, thereby killing the malaria parasites.
“The use of nanolipid drug carriers reduced the doses of the individual drugs by about 95% in both combinations of drugs in mice. This may address challenges such as the high toxicity of antimalarial drugs and help combat cerebral malaria,” says lead researcher Sulabha Pathak.
The authors of this work are from: Department of Biological Sciences and Atomic and Molecular Sciences Laboratory, Tata Institute of Fundamental Research and Institute of Chemical Technology, Mumbai, India.
1. Jain, S. A. et al. Parasite impairment by targeting Plasmodium-infected RBCs using glyceryl-dilaurate nanostructured lipid carriers. Biomaterials 35, 6636–6645 (2014)