title: An oral malaria therapy: curcumin-loaded lipid-based drug delivery systems combined with β-arteether.
abstract: Curcumin (CC), a potential antimalarial drug, has poor water solubility, stability and oral bioavailability. To circumvent these pitfalls, lipid-based drug delivery systems (LBDDSs) with a high CC loading (30 mg/g) were formulated. In a biorelevant gastric medium, CC-LBDDSs formed particle sizes in the range of 30-40 nm. During in vitro lipolysis, 90-95% of the CC remained solubilized, whereas 5-10% of the CC precipitated as an amorphous solid, with a high rate of re-dissolution in a biorelevant intestinal medium. The transport of the CC-LBDDS across Caco-2 monolayers was enhanced compared with the transport of free drug because of the increased CC solubility. In Plasmodium berghei-infected mice, modest antimalarial efficacy was observed following oral treatment with CC-LBDDSs. However, the combination therapy of CC-LBDDS with a subtherapeutic dose of β-arteether-LBDDS provided an increase in protection and survival rate that was associated with a significant delay in recrudescence. These findings suggest that the combination of oral CC and β-arteether lipid-based formulations may constitute a promising approach for the treatment of malaria.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and drug delivery group, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium; University of Kinshasa, Faculty of Pharmaceutical Sciences, Laboratoire de Pharmacie galénique, BP 212 Kinshasa XI, Democratic Republic of Congo.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Memvanga
authors.forename: Régis
authors.initials: R
authors.lastname: Coco
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage* / Q000627:therapeutic use; D018938:Caco-2 Cells; D003474:Curcumin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D008055:Lipids; D003474:Curcumin; C055141:artemotil
keywords: Antimalarial efficacy; Caco-2 cells; Curcumin; Lipid-based formulations; Oral delivery; β-arteether