Targeting Leishmania amazonensis amastigotes through macrophage internalisation of a hydroxymethylnitrofurazone nanostructured polymeric system

Detalhes bibliográficos
Autor(a) principal: Monteiro, Lis Marie
Data de Publicação: 2017
Outros Autores: Löbenberg, Raimar, Ferreira, Elizabeth Igne, Cotrim, Paulo Cesar, Kanashiro, Edite, Rocha, Mussya, Chung, Man Chin [UNESP], Bou-Chacra, Nadia
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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spelling 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
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