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 polyiso-hexylcyanoacrylate (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 tetrazo-lium (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.
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REFERENCES
C. R. Alving. Delivery of liposome-encapsulated drugs to macrophages. Pharmacol. Ther. 22:407–424 (1983).
V. Lenaerts, P. Couvreur, D. Christiaens-Leyh, E. Joiris, M. Roland, B. Rollman, and P. Speiser. Degradation of polyisobutylcyanoacrylate nanoparticles. Biomaterials 5:65–68 (1984).
B. Kante, P. Couvreur, G. Dubois-Crack, C. De Meester, and P. Guiot. Toxicity of polyalkylcyanoacrylate nanoparticles. I. Free nanoparticles. J. Pharm. Sci. 71:786–792 (1982).
P. Couvreur. Polyalkylcyanoacrylates as colloidal drug carriers. CRC Crit. Rev. Ther. Drug Carrier Syst. 5:1–20 (1988).
C. Verdun, P. Couvreur, H. Vranckx, V. Lenaerts, and M. Roland. Development of a nanoparticle controlled-release formulation for human use. J. Control. Release 3:205–210 (1986).
V. Lenaerts, J. F. Nagelkerke, T. J. C. Van Berkel, P. Couvreur, L. Grislain, M. Roland, and P. Speiser. In vivo uptake of polyisobutylcyanoacrylate nanoparticles by rat liver Küpffer, endothelial and parenchymal cells. J. Pharm. Sci. 59:980–982 (1984).
L. Grislain, P. Couvreur, V. Lenaerts, M. Roland, D. Deprez-Decampeneere, and P. Speiser. Pharmacokinetics and distribution of a biodegradable drug-carrier. Int. J. Pharm. 15:335–345 (1983).
R. Gaspar, V. Préat, and M. Roland. Nanoparticles of polyisohexylcyanoacrylate (PIHCA) as carriers of primaquine: Formulation, physico-chemical characterization and acute toxicity. Int. J. Pharm. 68:111–119 (1991).
R. Gaspar, F. R. Opperdoes, V. Préat, and M. Roland. Drug targeting with polyalkylcyanoacrylate nanoparticles: In vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani. Ann. Trop. Med. Parasitol., in press (1991).
A. Osuna Carillo de Albornoz and S. Castanys. Therapeutic agents in the form of submicroscopic particles against leishmaniases and pharmaceutical composition containing them. U.S. Patent 4,844,900 (1989).
C. Lherm, P. Couvreur, P. Loiseau, C. Bories, and P. Gayral. Unloaded polyisobutylcyanoacrylate: Efficiency against bloodstream trypanosomes. J. Pharm. Pharmacol. 39:650–652 (1987).
K.-P. Chang. Human cutaneous Leishmania in a mouse macrophage line: Propagation and isolation of intracellular parasites. Science 209:1240–1242 (1980).
H. W. Murray. Interaction of Leishmania with a macrophage cell line: Correlation between intracellular killing and the generation of oxygen intermediates. J. Exp. Med. 153:1690–1695 (1981).
D. T. Hart, W. J. Lauwers, G. Willemsems, H. V. Bossche, and F. R. Opperdoes. Perturbation of sterol biosynthesis by itraconazole and ketoconazole in Leishmania mexicana mexicana infected macrophages. Mol. Biochem. Parasitol. 33:123–134 (1989).
C. Lherm, R. Muller, J. Herbot, and P. Couvreur. Cytotoxicity of polyalkylcyanoacrylate particles of increasing alkyl chain length. 5th International Conference on Pharmaceutical Technology, III, 1989, pp. 81–88.
R. Brun and M. Schönenberger. Cultivation and in vitro cloning of procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Acta Trop. 36:289–292 (1979).
E. Pick. Microassays for superoxide and hydrogen peroxyde production and nitroblue tetrazolium reduction using an enzyme immunoassay microplate reader. Methods Enzymol. 132:407–421 (1986).
L. B. Lachman, L.-C. N. Shih, and D. C. Brown. Interleukin-1 from human leukemic monocytes. Methods Enzymol. 116:467–479 (1985).
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275 (1951).
H. W. Murray. Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. J. Exp. Med. 153:1302–1315 (1981).
R. D. Pearson and R. T. Steigbigel. Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes. J. Immunol. 127:1438–1443 (1981).
R. D. Pearson, J. L. Harcus, D. Roberts, and G. R. Donowitz. Differential survival of Leishmania donovani amastigotes in human monocytes. J. Immunol. 131:1994–1999 (1983).
N. E. Reiner and J. W. Kazura. Oxidant-mediated damage of Leishmania donovani promastigotes. Infect. Immuno. 36:1023–1027 (1982).
C. G. Haidaris and P. F. Bonventre. A role of oxygen-dependent mechanisms in killing of Leishmania donovani tissue forms by activated macrophages. J. Immunol. 129:850–855 (1982).
H. Murray and D. Cartelli. Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and independent leishmanicide activity. J. Clin. Invest. 72:32–44 (1983).
H. W. Murray. Cell-mediated response in experimental visceral leishmaniasis. 2. Oxygen-dependent killing of intracellular Leishmania donovani amastigotes. J. Immunol. 129:351–357 (1982).
N. E. Reiner. Parasite accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus-dependent suppression of the macrophage interleukin-1 response by Leishmania donovani. J. Immunol. 138:1919–1925 (1987).
H. Murray, B. Rubin, and C. Rothermel. Killing of intracellular Leishmania donovani by lymphokine stimulated human mononuclear phagocytes. Evidence that interferon γ is the activating lymphokine. J. Clin. Invest. 72:1506–1510 (1983).
P. Artursson, E. Arro, J. Ericsson, and I. Sjoholm. Biodegradable microspheres. V. Stimulation of macrophages with microparticles made of various polysaccharides. J. Pharm. Sci. 76:127–133 (1987).
P. Artursson, P. Edman, and J. Ericsson. Macrophage stimulation with some structurally related polysaccharides. Scand. J. Immunol. 25:245–254 (1987).
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Gaspar, R., Préat, V., Opperdoes, F.R. et al. Macrophage Activation by Polymeric Nanoparticles of Polyalkylcyanoacrylates: Activity Against Intracellular Leishmania donovani Associated with Hydrogen Peroxide Production. Pharm Res 9, 782–787 (1992). https://doi.org/10.1023/A:1015807706530
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DOI: https://doi.org/10.1023/A:1015807706530