Poly(D,L-lactic-co-glycolicacid)-based artesunate nanoparticles: formulation, antimalarial and toxicity assessments

The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment. Artesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei. Hematological and hepatic toxicity assays were performed. In vitro cytotoxicity of free and encapsulated artesunate (Art-PLGA) to cell line RAW 264.7 was determined at concentrations of 7.8-1000 mu g/ml. The particle size of the formulated drug was (329.3 +/- 21.7) nm and the entrapment efficiency was (38.4 +/- 10.1)%. Art-PLGA nanoparticles showed higher parasite suppression (62.6%) compared to free artesunate (58.2%, P < 0.05). Platelet counts were significantly higher in controls (305 000.00 +/- 148 492.40) than in mice treated with free artesunate (139 500.00 +/- 20 506.10) or Art-PLGA (163 500.00 +/- 3535.53) (P < 0.05). There was no sign of hepatic toxicity following use of the tested drugs. The half maximal inhibitory concentration (IC50) of Art-PLGA (468.0 mu g/ml) was significantly higher (P < 0.05) than that of free artesunate (7.3 mu g/ml) in the in vitro cytotoxicity assay. A simple treatment of PLGA-entrapped artesunate nanoparticles with dual advantages of low toxicity and better antiplasmodial efficacy has been developed.