Original Research ARTICLE
Sertraline Delivered in Phosphatidylserine Liposomes is Effective in Experimental Model of Visceral Leishmaniasis
- 1Adolfo Lutz Institute, Brazil
- 2Federal University of ABC, Brazil
- 3Oswaldo Cruz Foundation (Fiocruz), Brazil
- 4Center for Pathology, Instituto Adolfo Lutz, Brazil
- 5Independent researcher, Brazil
- 6University of Dundee, United Kingdom
- 7University of São Paulo, Brazil
Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage millie. Leishmania (L.) infantum parasites live inside macrophages and causes 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-labelled 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.
Keywords: Leishmania, Neglected Diseases, Drug Delievery, lipossomal formulation, drug repurposing, Sertraline
Received: 01 Jun 2019;
Accepted: 30 Sep 2019.
Copyright: © 2019 Romanelli, Costa Silva, Cunha-Junior, Dias Ferreira, Guerra, Galisteo Jr, Pinto, Barbosa, Torres-Santos and Tempone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Eduardo Caio Torres-Santos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, 21040-900, Rio de Janeiro, Brazil, email@example.com