Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity
Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative...
Published in: | Revista da Sociedade Brasileira de Medicina Tropical |
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Sociedade Brasileira de Medicina Tropical (SBMT)
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ftdoajarticles:oai:doaj.org/article:79fc984b79814b5f85d6af82b0f43b6c 2023-05-15T15:11:44+02:00 Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento 2016-04-01T00:00:00Z https://doi.org/10.1590/0037-8682-0041-2016 https://doaj.org/article/79fc984b79814b5f85d6af82b0f43b6c EN eng Sociedade Brasileira de Medicina Tropical (SBMT) http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196&lng=en&tlng=en https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0041-2016 https://doaj.org/article/79fc984b79814b5f85d6af82b0f43b6c Revista da Sociedade Brasileira de Medicina Tropical, Vol 49, Iss 2, Pp 196-203 (2016) Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine Arctic medicine. Tropical medicine RC955-962 article 2016 ftdoajarticles https://doi.org/10.1590/0037-8682-0041-2016 2022-12-30T21:26:05Z Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Revista da Sociedade Brasileira de Medicina Tropical 49 2 196 203 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine Arctic medicine. Tropical medicine RC955-962 |
spellingShingle |
Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine Arctic medicine. Tropical medicine RC955-962 Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
topic_facet |
Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine Arctic medicine. Tropical medicine RC955-962 |
description |
Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA) or pentavalent antimony salt (Sb) were obtained through filter extrusion (FEL) and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay). The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50) of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs. |
format |
Article in Journal/Newspaper |
author |
Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento |
author_facet |
Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento |
author_sort |
Samanta Etel Treiger Borborema |
title |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title_short |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title_full |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title_fullStr |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title_full_unstemmed |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title_sort |
antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
publisher |
Sociedade Brasileira de Medicina Tropical (SBMT) |
publishDate |
2016 |
url |
https://doi.org/10.1590/0037-8682-0041-2016 https://doaj.org/article/79fc984b79814b5f85d6af82b0f43b6c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Revista da Sociedade Brasileira de Medicina Tropical, Vol 49, Iss 2, Pp 196-203 (2016) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196&lng=en&tlng=en https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0041-2016 https://doaj.org/article/79fc984b79814b5f85d6af82b0f43b6c |
op_doi |
https://doi.org/10.1590/0037-8682-0041-2016 |
container_title |
Revista da Sociedade Brasileira de Medicina Tropical |
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49 |
container_issue |
2 |
container_start_page |
196 |
op_container_end_page |
203 |
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