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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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da Costa-Silva, Thais Alves ; Galisteo, Jr., Andres Jimenez ; Lauletta Lindoso, Jose Angelo ; Barbosa, Leandro R. S. ; Tempone, Andre Gustavo
Total Authors: 5
Document type: Journal article
Source: Antimicrobial Agents and Chemotherapy; v. 61, n. 4 APR 2017.
Web of Science Citations: 8

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. (AU)

FAPESP's process: 13/50228-8 - Biodiversity components, and its metabolic characters, of Brazilian Islands
Grantee:Roberto Gomes de Souza Berlinck
Support type: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 13/07275-5 - In vitro study of cellular immune response against synthetic drugs with antileishmanial activities
Grantee:Thaís Alves da Costa Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/15822-1 - Physicochemical and structural properties of ionic liquids and drugs interacting with biologicaly relevant systems
Grantee:Leandro Ramos Souza Barbosa
Support type: Regular Research Grants
FAPESP's process: 15/23403-9 - Rational pre-clinical study of new drug candidates against neglected protozoan diseases using pharmacokinetic approaches
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants