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Based on a drug repositioning approach, the aim of this work was to investigate the<jats:italic>in vitro<\/jats:italic>immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the<jats:italic>in vivo<\/jats:italic>efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in<jats:named-content content-type=\"genus-species\">Leishmania infantum<\/jats:named-content>-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the \u03b6-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<jats:italic>Leishmania<\/jats:italic>-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.<\/jats:p>","DOI":"10.1128\/aac.02297-16","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T01:50:11Z","timestamp":1486432211000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Thais Alves","family":"da Costa-Silva","sequence":"first","affiliation":[{"name":"Centre for Parasitology and Mycology, Instituto Adolfo Lutz, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.,","given":"Andr\u00e9s Jimenez","family":"Galisteo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Angelo Lauletta","family":"Lindoso","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Tropical, S\u00e3o Paulo, Brazil"},{"name":"Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro R. 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