Targeting intracellular Leishmania (L.) infantum with nitazoxanide entrapped into phosphatidylserine-nanoliposomes: An experimental study
| Autor: | Erika G. Pinto, Renato A. Mortara, Leandro R.S. Barbosa, Andre G. Tempone |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Nitazoxanide Static Electricity Antiprotozoal Agents Intracellular Space Phosphatidylserines Pharmacology Toxicology Article 03 medical and health sciences Inhibitory Concentration 50 0302 clinical medicine X-Ray Diffraction In vivo parasitic diseases Scattering Small Angle medicine Animals Leishmania infantum Amastigote Leishmania Mice Inbred BALB C biology Mesocricetus Chemistry Intracellular parasite Macrophages Macrophage interaction Leishmaniasis General Medicine biology.organism_classification medicine.disease Nitro Compounds Dynamic Light Scattering Thiazoles 030104 developmental biology Visceral leishmaniasis 030220 oncology & carcinogenesis Liposomes Nanoparticles Female Therapy Intracellular medicine.drug |
| Zdroj: | Chemico-Biological Interactions |
| ISSN: | 1872-7786 |
| Popis: | Leishmaniasis is a parasitic neglected tropical disease and result in a broad spectrum of clinical manifestations, ranging from a single ulceration to a progressive and fatal visceral disease. Comprising a limited and highly toxic therapeutic arsenal, new treatments are urgently needed. Targeting delivery of drugs has been a promising approach for visceral leishmaniasis (VL). Phosphatidylserine-liposomes have demonstrated superior efficacy in VL, targeting intracellular parasites in host cells through macrophage scavenger receptors. In this work, we investigated the in vitro and in vivo efficacy of the antihelminthic drug nitazoxanide in a nanoliposomal formulation against Leishmania (L.) infantum. Physicochemical parameters of liposomes containing nitazoxanide (NTZ-LP) were determined by dynamic light scattering and small angle X-ray scattering. The efficacy of the formulation was verified in an intracellular amastigote model and in an experimental hamster model. Our findings showed that NTZ-LP was able to eliminate the amastigotes inside the host cell with an IC50 value of 16 μM. NTZ-LP was labelled a fluorescent probe and by spectrofluorimetry, we observed that the infected macrophages internalized similar levels of the drug to the uninfected cells. The confocal microscopy images confirmed the uptake and demonstrated a diffuse distribution of the NTZ-LP in the cytoplasm of Leishmania-infected macrophages, with the vesicles in a closer proximity to the parasites. For the in vivo efficacy, the liposomal NTZ-LP was administrated intraperitoneally to Leishmania-infected hamsters for 10 consecutive days at 2 mg/kg/day. By qPCR we demonstrated a reduction of the parasite burden by 82% and 50% in the liver (p Graphical abstract Image 1 Highlights • Nanoliposomal nitazoxanide (NTZ-LP) eliminates amastigotes of Leishmania. • The uptake of NTZ-LP by infected macrophages is similar to uninfected cells. • NTZ-LP localizes in a closer proximity to the amastigotes inside the macrophages. • NTZ-LP reduces the parasite burden by 82% (liver) and 50% (spleen) of hamsters. |
| Databáze: | OpenAIRE |
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