Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Detalhes bibliográficos
Autor(a) principal: Petersen, Antonio Luis de Oliveira Almeida
Data de Publicação: 2018
Outros Autores: Campos, Thiers A, Dantas, Diana Angélica dos Santos, Rebouças, Juliana de Souza, Silva, Juliana Cruz da, Menezes, Juliana Perrone Bezerra de, Formiga, Fabio Rocha, Melo, Janaina V de, Machado, Giovanna, Veras, Patrícia Sampaio Tavares
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/29081
Resumo: Fundação de Amparo à Pesquisa do Estado da Bahia and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PV http:// www.fapesb.ba.gov.br, FAPESB.CAPES-PET 039.2013), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br, CNPq Universal 14/2013, Programa de Excelência em Pesquisa—PROEP/CPqGM). PV holds a grant from CNPq for productivity in research (307832/2015-5).
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spelling Petersen, Antonio Luis de Oliveira AlmeidaCampos, Thiers ADantas, Diana Angélica dos SantosRebouças, Juliana de SouzaSilva, Juliana Cruz daMenezes, Juliana Perrone Bezerra deFormiga, Fabio RochaMelo, Janaina V deMachado, GiovannaVeras, Patrícia Sampaio Tavares2018-09-26T17:13:47Z2018-09-26T17:13:47Z2018PETERSEN, A. L. O. A et al. Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages. Frontiers in Cellular and Infection Microbiology, v. 8, aug. 2018.2235-2988https://www.arca.fiocruz.br/handle/icict/2908110.3389/fcimb.2018.00303Fundação de Amparo à Pesquisa do Estado da Bahia and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PV http:// www.fapesb.ba.gov.br, FAPESB.CAPES-PET 039.2013), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br, CNPq Universal 14/2013, Programa de Excelência em Pesquisa—PROEP/CPqGM). PV holds a grant from CNPq for productivity in research (307832/2015-5).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilFederal University of Pernambuco. Center of Biological Sciences. Graduate Program in Biological Sciences. Recife, PE, Brazil / Center of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / University of Pernambuco. Institute of Biological Sciences. Recife, PE, BrazilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilUniversity of Pernambuco. Institute of Biological Sciences. Postgraduate Program in Applied Cellular and Molecular Biology. Recife, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laborátorio de Enfermedades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / National Institute of Technology in Tropical Diseases-National Council for Scientific and Technological Development. Brasilia, DF, BrazilThe current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro, while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis.engFrontiers Media17-AAGtanespimicina2-hidroxipropil-b-ciclodextrinaLipossomaSistemas de liberação de drogasLeishmanioseQuimioterapiaHSP-9017-AAGTanespimicyn2-hydroxypropyl-b-cyclodextrinLiposomedrug delivery systemsLeishmaniasisChemotherapyHSP-90Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophagesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz 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dc.title.pt_BR.fl_str_mv Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
title Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
spellingShingle Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
Petersen, Antonio Luis de Oliveira Almeida
17-AAG
tanespimicina
2-hidroxipropil-b-ciclodextrina
Lipossoma
Sistemas de liberação de drogas
Leishmaniose
Quimioterapia
HSP-90
17-AAG
Tanespimicyn
2-hydroxypropyl-b-cyclodextrin
Liposome
drug delivery systems
Leishmaniasis
Chemotherapy
HSP-90
title_short Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
title_full Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
title_fullStr Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
title_full_unstemmed Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
title_sort Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages
author Petersen, Antonio Luis de Oliveira Almeida
author_facet Petersen, Antonio Luis de Oliveira Almeida
Campos, Thiers A
Dantas, Diana Angélica dos Santos
Rebouças, Juliana de Souza
Silva, Juliana Cruz da
Menezes, Juliana Perrone Bezerra de
Formiga, Fabio Rocha
Melo, Janaina V de
Machado, Giovanna
Veras, Patrícia Sampaio Tavares
author_role author
author2 Campos, Thiers A
Dantas, Diana Angélica dos Santos
Rebouças, Juliana de Souza
Silva, Juliana Cruz da
Menezes, Juliana Perrone Bezerra de
Formiga, Fabio Rocha
Melo, Janaina V de
Machado, Giovanna
Veras, Patrícia Sampaio Tavares
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Petersen, Antonio Luis de Oliveira Almeida
Campos, Thiers A
Dantas, Diana Angélica dos Santos
Rebouças, Juliana de Souza
Silva, Juliana Cruz da
Menezes, Juliana Perrone Bezerra de
Formiga, Fabio Rocha
Melo, Janaina V de
Machado, Giovanna
Veras, Patrícia Sampaio Tavares
dc.subject.other.pt_BR.fl_str_mv 17-AAG
tanespimicina
2-hidroxipropil-b-ciclodextrina
Lipossoma
Sistemas de liberação de drogas
Leishmaniose
Quimioterapia
HSP-90
topic 17-AAG
tanespimicina
2-hidroxipropil-b-ciclodextrina
Lipossoma
Sistemas de liberação de drogas
Leishmaniose
Quimioterapia
HSP-90
17-AAG
Tanespimicyn
2-hydroxypropyl-b-cyclodextrin
Liposome
drug delivery systems
Leishmaniasis
Chemotherapy
HSP-90
dc.subject.en.pt_BR.fl_str_mv 17-AAG
Tanespimicyn
2-hydroxypropyl-b-cyclodextrin
Liposome
drug delivery systems
Leishmaniasis
Chemotherapy
HSP-90
description Fundação de Amparo à Pesquisa do Estado da Bahia and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PV http:// www.fapesb.ba.gov.br, FAPESB.CAPES-PET 039.2013), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br, CNPq Universal 14/2013, Programa de Excelência em Pesquisa—PROEP/CPqGM). PV holds a grant from CNPq for productivity in research (307832/2015-5).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-09-26T17:13:47Z
dc.date.available.fl_str_mv 2018-09-26T17:13:47Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv PETERSEN, A. L. O. A et al. Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages. Frontiers in Cellular and Infection Microbiology, v. 8, aug. 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/29081
dc.identifier.issn.pt_BR.fl_str_mv 2235-2988
dc.identifier.doi.none.fl_str_mv 10.3389/fcimb.2018.00303
identifier_str_mv PETERSEN, A. L. O. A et al. Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages. Frontiers in Cellular and Infection Microbiology, v. 8, aug. 2018.
2235-2988
10.3389/fcimb.2018.00303
url https://www.arca.fiocruz.br/handle/icict/29081
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
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