title: Drug targeting with polyalkylcyanoacrylate nanoparticles: in vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani.
abstract: The efficacy of primaquine-loaded polyisohexylcyanoacrylate (PIHCA) nanoparticles was evaluated using J774G8 macrophage-like cells infected with Leishmania donovani: as an in vitro model of visceral leishmaniasis. The in vitro antileishmanial activity of primaquine-loaded nanoparticles showed a 21-fold increase in ED50 compared with free primaquine. Although unloaded PIHCA nanoparticles also exhibited a significant anti-leishmanial effect, the loaded nanoparticles showed a synergistic effect compared with a mixture of unloaded nanoparticles and free primaquine at equivalent concentrations. Primaquine release and isohexanol production were evaluated in a lysosomal fraction; the correlation of both with protein concentration and the rapid drug release indicate the processes are associated with an enzymatic degradation. The results indicate that PIHCA and other polyalkylcyanoacrylates may be useful for targeting drugs at intracellular Leishmania, and that the unloaded carrier itself could be of interest in experimental chemotherapy of leishmaniasis.
authors.affiliation: Laboratoire de Pharmacie Galénique, Université Catholique de Louvain, Bruxelles, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Gaspar
authors.forename: F R
authors.initials: FR
authors.lastname: Opperdoes
authors.forename: V
authors.initials: V
authors.lastname: Préat
authors.forename: M
authors.initials: M
authors.lastname: Roland
mesh_terms: D000818:Animals; D002460:Cell Line; D003487:Cyanoacrylates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D066298:In Vitro Techniques; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D011319:Primaquine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D003487:Cyanoacrylates; D004337:Drug Carriers; C057532:polyisohexylcyanoacrylate; D011319:Primaquine