Nanoparticle formulations of decoquinate increase antimalarial efficacy against liver stage Plasmodium infections in mice.

Decoquinate has potent activity against both Plasmodium hepatic development and red cell replication when tested in vitro. Decoquinate, however, is practically insoluble in water. To achieve its maximal in vivo efficacy, we generated nanoparticle formulations of decoquinate with a mean particle size less than 400nm. Three separate preparations at doses of decoquinate 0.5-5mg/kg were examined in mice infected with Plasmodium berghei. Oral administration of nanoparticle decoquinate at a dose of 1.25mg/kg effectively inhibited the liver-stage parasite growth and provided complete causal prophylactic protection. This efficacy is 15 fold greater than that observed for microparticle decoquinate, which requires minimal dose of 20mg/kg for the same inhibitory effect. Further in vitro studies utilizing dose–response assays revealed that decoquinate nanoformulation was substantially more potent than decoquinate microsuspension in killing both liver and blood stage malarial parasites, proving its potential for therapeutic development.