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 400 nm. Three separate preparations at doses of decoquinate 0.5-5 mg/kg were examined in mice infected with Plasmodium berghei. Oral administration of nanoparticle decoquinate at a dose of 1.25 mg/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 20 mg/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.From the Clinical EditorIn this study, a nanoparticle formulation of decoquinate is shown to have superior bioavailability and efficacy in a mouse model of malaria, paving the way to the development of novel, potentially less toxic and more effective therapeutics to combat a disease that still has an enormous impact on a global scale despite the available partially effective therapies.

Graphical AbstractThe life cycle of malaria parasites includes both a blood stage and liver stage. The liver stage is an early phase of the life cycle, and intervention at this stage when the parasite burden is low is desirable for both prophylaxis and treatment. Due to increased bioavailability and tissue penetration, decoquinate nanoparticle formulations presented in this article effectively inhibit liver stage Plasmodium berghei and provide a complete causal prophylactic protection from Plasmodium infection. Furthermore, if any residual parasites in the form of gametocytes remain, decoquinate could potentially act on killing them, interrupting the transmission of malarial parasites from patients to mosquitoes through mosquito bites.Figure optionsDownload high-quality image (54 K)Download as PowerPoint slide