Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation

摘要

Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5?nm and polydispersity index of 0.172±0.01 were produced in ? DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900?μg/mL compared to the raw ARTM in water (145.0±2.3?μg/mL) and stabilizer solution (300.0±2.0?μg/mL). The physical stability studies conducted for 90?days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased ( P 50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC₅₀ value of unprocessed drug and 13- and 21-fold lower than the IC₅₀ value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2?mg/kg) showed significantly ( P 50 value of ARTM nanocrystals is between 1,500?mg/kg and 2,000?mg/kg when given orally. This study demonstrated that the wet milling technology (Dena? DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.