Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Revista da Sociedade Brasileira de Medicina Tropical |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196 |
Resumo: | 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. |
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Revista da Sociedade Brasileira de Medicina Tropical |
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Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activityAntimonyLeishmania infantumLiposomeMeglumine antimoniatePhosphatidylserineAbstract: 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.Sociedade Brasileira de Medicina Tropical - SBMT2016-04-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196Revista da Sociedade Brasileira de Medicina Tropical v.49 n.2 2016reponame:Revista da Sociedade Brasileira de Medicina Tropicalinstname:Sociedade Brasileira de Medicina Tropical (SBMT)instacron:SBMT10.1590/0037-8682-0041-2016info:eu-repo/semantics/openAccessBorborema,Samanta Etel TreigerOsso Junior,João AlbertoAndrade Junior,Heitor Franco deNascimento,Nanci doeng2016-09-14T00:00:00Zoai:scielo:S0037-86822016000200196Revistahttps://www.sbmt.org.br/portal/revista/ONGhttps://old.scielo.br/oai/scielo-oai.php||dalmo@rsbmt.uftm.edu.br|| rsbmt@rsbmt.uftm.edu.br1678-98490037-8682opendoar:2016-09-14T00:00Revista da Sociedade Brasileira de Medicina Tropical - Sociedade Brasileira de Medicina Tropical (SBMT)false |
dc.title.none.fl_str_mv |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
title |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity |
spellingShingle |
Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity Borborema,Samanta Etel Treiger Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine |
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 |
author |
Borborema,Samanta Etel Treiger |
author_facet |
Borborema,Samanta Etel Treiger Osso Junior,João Alberto Andrade Junior,Heitor Franco de Nascimento,Nanci do |
author_role |
author |
author2 |
Osso Junior,João Alberto Andrade Junior,Heitor Franco de Nascimento,Nanci do |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Borborema,Samanta Etel Treiger Osso Junior,João Alberto Andrade Junior,Heitor Franco de Nascimento,Nanci do |
dc.subject.por.fl_str_mv |
Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine |
topic |
Antimony Leishmania infantum Liposome Meglumine antimoniate Phosphatidylserine |
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. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-04-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822016000200196 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/0037-8682-0041-2016 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Medicina Tropical - SBMT |
publisher.none.fl_str_mv |
Sociedade Brasileira de Medicina Tropical - SBMT |
dc.source.none.fl_str_mv |
Revista da Sociedade Brasileira de Medicina Tropical v.49 n.2 2016 reponame:Revista da Sociedade Brasileira de Medicina Tropical instname:Sociedade Brasileira de Medicina Tropical (SBMT) instacron:SBMT |
instname_str |
Sociedade Brasileira de Medicina Tropical (SBMT) |
instacron_str |
SBMT |
institution |
SBMT |
reponame_str |
Revista da Sociedade Brasileira de Medicina Tropical |
collection |
Revista da Sociedade Brasileira de Medicina Tropical |
repository.name.fl_str_mv |
Revista da Sociedade Brasileira de Medicina Tropical - Sociedade Brasileira de Medicina Tropical (SBMT) |
repository.mail.fl_str_mv |
||dalmo@rsbmt.uftm.edu.br|| rsbmt@rsbmt.uftm.edu.br |
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1752122160184295424 |