Formulation design and in vivo antimalarial evaluation of lipid-based drug delivery systems for oral delivery of β-arteether

β-Arteether, an effective artemisinin derivative, is used in the treatment of malaria but available only as an intramuscular injection. The objective of this work was to develop lipid-based formulations for oral administration of β-arteether. Self-emulsifying drug delivery systems (SEDDSs) of low cost and with accessible excipients (groundnut or sesame oil, Maisine 35-1, Tween 80 or Cremophor EL, and absolute ethanol) were formulated. In 250 ml of simulated gastric medium, 1 g of these SEDDS solubilized the daily dose of β-arteether and formed lipid droplets of average size 80–250 nm. No toxicity against Caco-2 intestinal cells was observed. Using a mouse model, the efficacy of these arteether lipid formulations against Plasmodium berghei was evaluated. A daily dose of 24 mg/kg for 4 days led to complete cure for more than 45 days in 100% of treated mice and had an antimalarial efficacy comparable to that of an intramuscular oily solution of arteether and significantly higher than that of an oily solution of β-arteether given orally at the same dose. In conclusion, lipid-based drug delivery systems constitute a promising approach for the oral administration of β-arteether.

Graphical abstractSelf-emulsifying lipid-based formulations containing β-arteether enhance the solubility and stability of the drug in gastrointestinal medium and are active against Plasmodium berghei after oral delivery in mice.Figure optionsDownload full-size imageDownload high-quality image (72 K)Download as PowerPoint slide