title: "Squalenoylcurcumin" nanoassemblies as water-dispersible drug candidates with antileishmanial activity.
abstract: Curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. The molecule is well tolerated in humans. However, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. New derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1',2-tris-norsqualenic acid. These "squalenoylcurcumins" were formulated as water-dispersible nanoassemblies of homogeneous size, and they proved to be stable. Squalenoylcurcumins were inactive against Trypanosoma brucei brucei trypomastigotes, even as nanoassemblies, in contrast with curcumin. However, against Leishmania donovani promastigotes, the activities of the squalenoylcurcumins and their nanoassemblies were enhanced relative to that of curcumin. In L. donovani axenic and intramacrophagic amastigotes, they showed activity in the range of miltefosine, with good selectivity indexes. In regard to their dispersibility in water and to the safety of curcumin, these nanoassemblies are promising candidates for preclinical study toward the treatment of visceral leishmaniasis.
authors.affiliation: Laboratoire de Pharmacognosie, CNRS UMR 8076 BioCIS, LabEX LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry (France).
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Cheikh-Ali
authors.forename: Joachim
authors.initials: J
authors.lastname: Caron
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cojean
authors.forename: Christian
authors.initials: C
authors.lastname: Bories
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.forename: Erwan
authors.initials: E
authors.lastname: Poupon
authors.forename: Pierre
authors.initials: P
authors.lastname: Champy
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004951:Esterification; D007893:Leishmania donovani / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D014867:Water; D003474:Curcumin
keywords: biological activity; curcumin; drug discovery; nanoparticles; squalenoylation