title: Formulation design and in vivo antimalarial evaluation of lipid-based drug delivery systems for oral delivery of β-arteether.
abstract: 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, 1g 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.
authors.affiliation: Pharmaceutics and Drug Delivery Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Memvanga
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D037621:Artemisinins / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008055:Lipids; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei / Q000302:isolation & purification; D012995:Solubility
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004655:Emulsions; D005079:Excipients; D008055:Lipids; C055141:artemotil