期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 134, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.111120
关键词
Fullerol; Fullerenol; Liposomes; Leishmaniasis; Immunomodulation; Drug delivery
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [305659/2017-0, 425332/2018-7]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [RED-00007-14, APQ-03129-16]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
The study found that fullerol has potential anti-leishmanial activity, especially when combined with liposomes, showing significant reduction in parasite load. This innovative approach provides a new potential method for treating VL.
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-alpha, IFN-gamma and IL-1 beta 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.
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