Sertraline Delivered in Phosphatidylserine Liposomes Is Effective in an Experimental Model of Visceral Leishmaniasis

Abstract

Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. Leishmania (L.) infantum parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment. Sertraline was studied as a free formulation (SERT) and also entrapped into phosphatidylserine liposomes (LP-SERT) against intracellular amastigotes and in a murine model of visceral leishmaniasis. LP-SERT showed a potent activity against intracellular amastigotes with an EC50 value of 2.5 μM. The in vivo efficacy of SERT demonstrated a therapeutic failure. However, when entrapped into negatively charged liposomes (−58 mV) of 125 nm, it significantly reduced the parasite burden in the mice liver by 89% at 1 mg/kg, reducing the serum levels of the cytokine IL-6 and upregulating the levels of the chemokine MCP-1. Histopathological studies demonstrated the presence of an inflammatory infiltrate with the development of granulomas in the liver, suggesting the resolution of the infection in the treated group. Delivery studies showed fluorescent-labeled LP-SERT in the liver and spleen of mice even after 48 h of administration. This study demonstrates the efficacy of PS liposomes containing sertraline in experimental VL. Considering the urgent need for VL treatments, the repurposing approach of SERT could be a promising alternative.

An overview of the treatment of cutaneous leishmaniasis

“…assessed the efficacy of sertraline entrapped in phosphatidylserine liposomes (LP-SERT) in a murine model of visceral leishmaniasis. This treatment was able to reduce the liver parasite burden by 72% at 0.3 mg/kg ( P <0.05) and by 89% at 1 mg/kg ( P <0.05) when compared with the placebo group (only liposomes), who experienced no effect 45 .…”

Targeting intracellular Leishmania (L.) infantum with nitazoxanide entrapped into phosphatidylserine-nanoliposomes: An experimental study

“…Non-infected macrophages were used as control. After 24 h of incubation, liposomal nitazoxanide labelled with the fluorescent probe DIL C18 (NTZ-LP-DIL) and the uptake was monitored in a spectrofluorimeter (FilterMax 5 Molecular Devices) every 15 min over 360 min, using excitation and emission filters of 549 and 565 nm, respectively [ 26 ].…”

“…D h is related to the translational diffusional dynamics of the vesicle, and can be written using the Stokes-Einstein relationships, as follows:where k B is the Boltzmann constant, T is the absolute temperature, η is the viscosity of the solvent, D h and D app are the hydrodynamic diameter and the apparent translational diffusion coefficient, respectively [ 26 ].…”

“…The measurement for each sample was repeated for at least three times. In order to avoid multiple scattering, similar to DLS measurements, samples were diluted at least 20-fold, in the appropriate buffer before the measurements [ 26 ].…”

Short-Course Treatment With Imipramine Entrapped in Squalene Liposomes Results in Sterile Cure of Experimental Visceral Leishmaniasis Induced by Antimony Resistant Leishmania donovani With Increased Efficacy

“…Liposomal formulation of antimonials are also more effective in leishmaniasis (Alving et al, 1978;Borborema et al, 2016). Recently, antidepressant-Sertraline delivered in phosphatidylserine liposomes has shown effectiveness in an experimental model of VL (Romanelli et al, 2019).…”