Advanced search
Start date
Betweenand
(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

Full text
Author(s):
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: 5
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. (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