Pharmaceutica Analytica Acta

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

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Hongxing Wang

Posters & Accepted Abstracts: Pharm Anal Acta

Abstract:

Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. 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 nano formulation was substantially more potent than decoquinate microsuspension in killing both liver and blood stage malarial parasites, proving its potential for therapeutic development.