Antileishmanial activity of fullerol and its liposomal formulation in experimental models of visceral leishmaniasis

[Display omitted] •First report of antileishmanial activity of fullerol.•Fullerol reduces hepatic parasite load in murine model of visceral leishmaniasis.•Liposome encapsulation of fullerol enhances its antileishmanial activity in vivo.•An innovative therapeutic approach based on the association of...

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Published in:	Biomedicine & pharmacotherapy Vol. 134; p. 111120
Main Authors:	Ramos, Guilherme S., Vallejos, Virgínia M.R., Ladeira, Marina S., Reis, Priscila G., Souza, Daniel M., Machado, Yuri A., Ladeira, Luiz O., Pinheiro, Maurício B.V., Melo, Maria N., Fujiwara, Ricardo T., Frézard, Frédéric
Format:	Journal Article
Language:	English
Published:	France Elsevier Masson SAS 01-02-2021 Elsevier
Subjects:	Animals Cytokines - blood Disease Models, Animal Drug Compounding Drug delivery Female Fullerenes - chemistry Fullerenes - pharmacology Fullerenol Fullerol Immunomodulation Inflammation Mediators - blood Leishmania infantum - drug effects Leishmania infantum - growth & development Leishmania mexicana - drug effects Leishmania mexicana - growth & development Leishmaniasis Leishmaniasis, Visceral - blood Leishmaniasis, Visceral - drug therapy Leishmaniasis, Visceral - parasitology Lipids - chemistry Liposomes Liver - metabolism Liver - parasitology Macrophages, Peritoneal - parasitology Mesocricetus Mice Mice, Inbred BALB C Nanoparticles Parasite Load Trypanocidal Agents - chemistry Trypanocidal Agents - pharmacology Fullerol Fullerenol Drug delivery Liposomes Leishmaniasis Immunomodulation
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Summary:	[Display omitted] •First report of antileishmanial activity of fullerol.•Fullerol reduces hepatic parasite load in murine model of visceral leishmaniasis.•Liposome encapsulation of fullerol enhances its antileishmanial activity in vivo.•An innovative therapeutic approach based on the association of two nanosystems. Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC50 of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1β cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes.
ISSN:	0753-3322 1950-6007
DOI:	10.1016/j.biopha.2020.111120