Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.ijantimicag.2017.01.033 http://hdl.handle.net/11449/177008 |
Resumo: | Dextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared and were evaluated for enhanced delivery of a promising anti-Leishmania drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently available chemotherapy for leishmaniasis, such as pentavalent antimonials, presents low safety and efficacy. Furthermore, widespread drug resistance in leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of nanosized delivery systems can reduce systemic drug toxicity and increase the drug concentration in infected macrophages, therefore improving treatment of leishmaniasis. PBCA-NPs containing NFOH (PBCA–NFOH-NPs) were prepared by an anionic emulsion polymerisation method. The z-average and polydispersity index (PDI) were determined by photon correlation spectroscopy, the zeta potential by microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was determined using macrophages from BALB/c mice. Efficacy tests were performed using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA–NFOH-NPs was 151.5 ± 61.97 nm, with a PDI of 0.104 ± 0.01, a zeta potential of −10.1 ± 6.49 mV and an entrapment efficiency of 64.47 ± 0.43%. Efficacy in amastigotes revealed IC50 values of 0.33 µM and 31.2 µM for the nanostructured and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated low toxicity of the PBCA–NFOH-NPs to macrophages. The selectivity index was 370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that improved efficacy could be due to NP internalisation following site-specific drug delivery and reactivation of immune protective reactions by the NP components. Thus, PBCA–NFOH-NPs have the potential to significantly improve the treatment of leishmaniasis, with reduced systemic side effects. |
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Repositório Institucional da UNESP |
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Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric systemDextranDrug deliveryHydroxymethylnitrofurazoneLeishmaniasisPoly (n-butyl cyanoacrylate)Polymeric nanoparticlesDextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared and were evaluated for enhanced delivery of a promising anti-Leishmania drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently available chemotherapy for leishmaniasis, such as pentavalent antimonials, presents low safety and efficacy. Furthermore, widespread drug resistance in leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of nanosized delivery systems can reduce systemic drug toxicity and increase the drug concentration in infected macrophages, therefore improving treatment of leishmaniasis. PBCA-NPs containing NFOH (PBCA–NFOH-NPs) were prepared by an anionic emulsion polymerisation method. The z-average and polydispersity index (PDI) were determined by photon correlation spectroscopy, the zeta potential by microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was determined using macrophages from BALB/c mice. Efficacy tests were performed using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA–NFOH-NPs was 151.5 ± 61.97 nm, with a PDI of 0.104 ± 0.01, a zeta potential of −10.1 ± 6.49 mV and an entrapment efficiency of 64.47 ± 0.43%. Efficacy in amastigotes revealed IC50 values of 0.33 µM and 31.2 µM for the nanostructured and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated low toxicity of the PBCA–NFOH-NPs to macrophages. The selectivity index was 370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that improved efficacy could be due to NP internalisation following site-specific drug delivery and reactivation of immune protective reactions by the NP components. Thus, PBCA–NFOH-NPs have the potential to significantly improve the treatment of leishmaniasis, with reduced systemic side effects.Pharmacy Department Faculty of Pharmaceutical Sciences University de São PauloFaculty of Pharmacy and Pharmaceutical Sciences University of AlbertaSeroepidemiology Cellular and Molecular Immunology Laboratory Institute of Tropical Medicine University of São PauloFaculty of Pharmaceutical Sciences UNESP–AraraquaraFaculty of Pharmaceutical Sciences UNESP–AraraquaraUniversity de São PauloUniversity of AlbertaUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Monteiro, Lis MarieLöbenberg, RaimarFerreira, Elizabeth IgneCotrim, Paulo CesarKanashiro, EditeRocha, MussyaChung, Man Chin [UNESP]Bou-Chacra, Nadia2018-12-11T17:23:29Z2018-12-11T17:23:29Z2017-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article88-92application/pdfhttp://dx.doi.org/10.1016/j.ijantimicag.2017.01.033International Journal of Antimicrobial Agents, v. 50, n. 1, p. 88-92, 2017.1872-79130924-8579http://hdl.handle.net/11449/17700810.1016/j.ijantimicag.2017.01.0332-s2.0-850191345822-s2.0-85019134582.pdf97343336079754130000-0003-4141-0455Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Antimicrobial Agents1,699info:eu-repo/semantics/openAccess2023-10-30T06:09:53Zoai:repositorio.unesp.br:11449/177008Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:27:10.450863Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
title |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
spellingShingle |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system Monteiro, Lis Marie Dextran Drug delivery Hydroxymethylnitrofurazone Leishmaniasis Poly (n-butyl cyanoacrylate) Polymeric nanoparticles |
title_short |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
title_full |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
title_fullStr |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
title_full_unstemmed |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
title_sort |
Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system |
author |
Monteiro, Lis Marie |
author_facet |
Monteiro, Lis Marie Löbenberg, Raimar Ferreira, Elizabeth Igne Cotrim, Paulo Cesar Kanashiro, Edite Rocha, Mussya Chung, Man Chin [UNESP] Bou-Chacra, Nadia |
author_role |
author |
author2 |
Löbenberg, Raimar Ferreira, Elizabeth Igne Cotrim, Paulo Cesar Kanashiro, Edite Rocha, Mussya Chung, Man Chin [UNESP] Bou-Chacra, Nadia |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
University de São Paulo University of Alberta Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Monteiro, Lis Marie Löbenberg, Raimar Ferreira, Elizabeth Igne Cotrim, Paulo Cesar Kanashiro, Edite Rocha, Mussya Chung, Man Chin [UNESP] Bou-Chacra, Nadia |
dc.subject.por.fl_str_mv |
Dextran Drug delivery Hydroxymethylnitrofurazone Leishmaniasis Poly (n-butyl cyanoacrylate) Polymeric nanoparticles |
topic |
Dextran Drug delivery Hydroxymethylnitrofurazone Leishmaniasis Poly (n-butyl cyanoacrylate) Polymeric nanoparticles |
description |
Dextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared and were evaluated for enhanced delivery of a promising anti-Leishmania drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently available chemotherapy for leishmaniasis, such as pentavalent antimonials, presents low safety and efficacy. Furthermore, widespread drug resistance in leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of nanosized delivery systems can reduce systemic drug toxicity and increase the drug concentration in infected macrophages, therefore improving treatment of leishmaniasis. PBCA-NPs containing NFOH (PBCA–NFOH-NPs) were prepared by an anionic emulsion polymerisation method. The z-average and polydispersity index (PDI) were determined by photon correlation spectroscopy, the zeta potential by microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was determined using macrophages from BALB/c mice. Efficacy tests were performed using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA–NFOH-NPs was 151.5 ± 61.97 nm, with a PDI of 0.104 ± 0.01, a zeta potential of −10.1 ± 6.49 mV and an entrapment efficiency of 64.47 ± 0.43%. Efficacy in amastigotes revealed IC50 values of 0.33 µM and 31.2 µM for the nanostructured and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated low toxicity of the PBCA–NFOH-NPs to macrophages. The selectivity index was 370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that improved efficacy could be due to NP internalisation following site-specific drug delivery and reactivation of immune protective reactions by the NP components. Thus, PBCA–NFOH-NPs have the potential to significantly improve the treatment of leishmaniasis, with reduced systemic side effects. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-07-01 2018-12-11T17:23:29Z 2018-12-11T17:23:29Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.ijantimicag.2017.01.033 International Journal of Antimicrobial Agents, v. 50, n. 1, p. 88-92, 2017. 1872-7913 0924-8579 http://hdl.handle.net/11449/177008 10.1016/j.ijantimicag.2017.01.033 2-s2.0-85019134582 2-s2.0-85019134582.pdf 9734333607975413 0000-0003-4141-0455 |
url |
http://dx.doi.org/10.1016/j.ijantimicag.2017.01.033 http://hdl.handle.net/11449/177008 |
identifier_str_mv |
International Journal of Antimicrobial Agents, v. 50, n. 1, p. 88-92, 2017. 1872-7913 0924-8579 10.1016/j.ijantimicag.2017.01.033 2-s2.0-85019134582 2-s2.0-85019134582.pdf 9734333607975413 0000-0003-4141-0455 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Antimicrobial Agents 1,699 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
88-92 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128654211809280 |