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

Autor: Maiara M. Romanelli, Eduardo Caio Torres-Santos, Andrés Jimenez Galisteo, Juliana Mariotti Guerra, Thais A. Costa-Silva, Erika G. Pinto, Daiane D. Ferreira, Leandro R.S. Barbosa, Edézio Ferreira Cunha-Júnior, Andre G. Tempone
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Microbiology (medical)
liposomes
Chemokine
030106 microbiology
Immunology
Antiprotozoal Agents
lcsh:QR1-502
Spleen
Phosphatidylserines
Pharmacology
Microbiology
lcsh:Microbiology
Immunomodulation
Mice
03 medical and health sciences
chemistry.chemical_compound
Cellular and Infection Microbiology
leishmania
In vivo
neglected diseases
medicine
Animals
Original Research
Mice
Inbred BALB C
Liposome
Dose-Response Relationship
Drug
biology
drug repurposing
sertraline
Macrophages
Phosphatidylserine
Leishmania
biology.organism_classification
medicine.disease
Disease Models
Animal
030104 developmental biology
Infectious Diseases
Visceral leishmaniasis
medicine.anatomical_structure
Liver
chemistry
Drug delivery
drug delivery
biology.protein
Leishmaniasis
Visceral
Female
Leishmania donovani
Zdroj: Frontiers in Cellular and Infection Microbiology, Vol 9 (2019)
Frontiers in Cellular and Infection Microbiology
ISSN: 2235-2988
DOI: 10.3389/fcimb.2019.00353/full
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: