title: Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production.
abstract: Nanoparticles of polyalkylcyanoacrylates (PACA) can be useful carrier for the targeting of antileishmanial drugs into macrophages and also possess significant antileishmanial activity by themselves. No significant difference in antileishmanial activity could be detected between nanoparticles of five PACAs with differing alkyl side chains, suggesting that the main degradation products of PACA are not involved in their antileishmanial action. The effect of polyisohexylcyanoacrylate (PIHCA) on the induction of the respiratory burst in a macrophage-like cell line (J774G8) was assessed in non-infected macrophages and in macrophages infected with amastigotes of Leishmania donovani infantum, by measuring nitroblue tetrazolium (NBT) reduction and hydrogen peroxide production. Phagocytosis of PIHCA nanoparticles led to a respiratory burst, which was more pronounced in infected than in uninfected macrophages. The production of reactive oxygen intermediates associated with the respiratory burst was inhibited by addition of superoxide dismutase and catalase to the cell suspensions. The addition of catalase to the culture medium together with PIHCA nanoparticles significantly reduced the antileishmanial activity of PIHCA. Moreover PIHCA nanoparticles did not induce interleukin-1 release by macrophages. It is suggested that the antileishmanial action of PIHCA and other PACA nanoparticles results from the activation of respiratory burst in macrophages.
authors.affiliation: Laboratoire de Pharmacie Galénique, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Gaspar
authors.forename: V
authors.initials: V
authors.lastname: Préat
authors.forename: F R
authors.initials: FR
authors.lastname: Opperdoes
authors.forename: M
authors.initials: M
authors.lastname: Roland
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003487:Cyanoacrylates / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D009580:Nitroblue Tetrazolium / Q000378:metabolism
chemical_list: D003487:Cyanoacrylates; D004337:Drug Carriers; D007375:Interleukin-1; C057532:polyisohexylcyanoacrylate; D009580:Nitroblue Tetrazolium; D006861:Hydrogen Peroxide; D002374:Catalase