Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/13031 |
Resumo: | Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved. |
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Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticlesAlveolar macrophagesPhysicochemical propertiesIn-vitroNanoparticlesPowderFormulationsChitosanDesignInhalationDepositionDespite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.National Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011]ElsevierSapientiaRodrigues, SusanaAlves, Ana D.Cavaco, Joana S.Pontes, Jorge FilipeGuerreiro, FilipaRosa Da Costa, AnaButtini, FrancescaGrenha, Ana2019-11-20T15:07:25Z2017-082017-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/13031eng0378-517310.1016/j.ijpharm.2017.06.088info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:25:03Zoai:sapientia.ualg.pt:10400.1/13031Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:04:15.041624Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
title |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
spellingShingle |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles Rodrigues, Susana Alveolar macrophages Physicochemical properties In-vitro Nanoparticles Powder Formulations Chitosan Design Inhalation Deposition |
title_short |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
title_full |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
title_fullStr |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
title_full_unstemmed |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
title_sort |
Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles |
author |
Rodrigues, Susana |
author_facet |
Rodrigues, Susana Alves, Ana D. Cavaco, Joana S. Pontes, Jorge Filipe Guerreiro, Filipa Rosa Da Costa, Ana Buttini, Francesca Grenha, Ana |
author_role |
author |
author2 |
Alves, Ana D. Cavaco, Joana S. Pontes, Jorge Filipe Guerreiro, Filipa Rosa Da Costa, Ana Buttini, Francesca Grenha, Ana |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Rodrigues, Susana Alves, Ana D. Cavaco, Joana S. Pontes, Jorge Filipe Guerreiro, Filipa Rosa Da Costa, Ana Buttini, Francesca Grenha, Ana |
dc.subject.por.fl_str_mv |
Alveolar macrophages Physicochemical properties In-vitro Nanoparticles Powder Formulations Chitosan Design Inhalation Deposition |
topic |
Alveolar macrophages Physicochemical properties In-vitro Nanoparticles Powder Formulations Chitosan Design Inhalation Deposition |
description |
Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08 2017-08-01T00:00:00Z 2019-11-20T15:07:25Z |
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://hdl.handle.net/10400.1/13031 |
url |
http://hdl.handle.net/10400.1/13031 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0378-5173 10.1016/j.ijpharm.2017.06.088 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133278313119744 |