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 ζ-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