Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author COSTA-SILVA, Thais Alves da
GALISTEO JR., Andres Jimenez FMUSP-HC
LINDOSO, Jose Angelo Lauletta FMUSP-HC
BARBOSA, Leandro R. S.
TEMPONE, Andre Gustavo
dc.date.issued 2017
dc.identifier.citation ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, v.61, n.4, article ID UNSP e02297, 15p, 2017
dc.identifier.issn 0066-4804
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/20375
dc.description.abstract Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in Leishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the zeta-potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 in Leishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.
dc.description.sponsorship · CNPq
· GlaxoSmithKline
· Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2015/23403-9, 2015/15822-1, 2013/07275-5, 2013/50228-8]
dc.language.iso eng
dc.publisher AMER SOC MICROBIOLOGY
dc.relation.ispartof Antimicrobial Agents and Chemotherapy
dc.rights restrictedAccess
dc.subject Leishmania; drug delivery; liposomes; therapy
dc.subject.other visceral leishmaniasis; cutaneous leishmaniasis; mice lacking; bone-marrow; l. chagasi; in-vitro; liposomes; donovani; size; phagocytosis
dc.title Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model
dc.type article
dc.rights.holder Copyright AMER SOC MICROBIOLOGY
dc.description.group LIM/49
dc.description.group LIM/38
dc.identifier.doi 10.1128/AAC.02297-16
dc.identifier.pmid 28167544
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author GALISTEO JR., Andres Jimenez:HC:LIM/49
hcfmusp.author LINDOSO, Jose Angelo Lauletta:HC:LIM/38
hcfmusp.author.external · COSTA-SILVA, Thais Alves da:Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo, Brazil
· BARBOSA, Leandro R. S.:Univ Sao Paulo, Inst Fis, Sao Paulo, Brazil
· TEMPONE, Andre Gustavo:Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo, Brazil
hcfmusp.origem.id 2-s2.0-85017034589
hcfmusp.origem.id WOS:000397598800042
hcfmusp.publisher.city WASHINGTON
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
dc.identifier.eissn 1098-6596
hcfmusp.citation.scopus 3
hcfmusp.citation.wos 3


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