Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/10400.1/11510 |
Resumo: | The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis. |
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Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapyDry Powder InhalersAlveolar MacrophagesAerodynamic PerformanceIn-VitroDeliveryRifabutinRifampicinPolysaccharidesNanoparticlesMicrospheresThe pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4]MDPISapientiaCunha, Ludmylla CostaRodrigues, SusanaRosa Da Costa, AnaFaleiro, Maria LeonorButtini, FrancescaGrenha, Ana2018-12-07T14:53:25Z2018-062018-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11510eng2073-436010.3390/polym10060636info: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:RCAAP2023-07-24T10:23:19Zoai:sapientia.ualg.pt:10400.1/11510Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:00.356531Repositório 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 |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
title |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
spellingShingle |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy Cunha, Ludmylla Costa Dry Powder Inhalers Alveolar Macrophages Aerodynamic Performance In-Vitro Delivery Rifabutin Rifampicin Polysaccharides Nanoparticles Microspheres |
title_short |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
title_full |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
title_fullStr |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
title_full_unstemmed |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
title_sort |
Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy |
author |
Cunha, Ludmylla Costa |
author_facet |
Cunha, Ludmylla Costa Rodrigues, Susana Rosa Da Costa, Ana Faleiro, Maria Leonor Buttini, Francesca Grenha, Ana |
author_role |
author |
author2 |
Rodrigues, Susana Rosa Da Costa, Ana Faleiro, Maria Leonor Buttini, Francesca Grenha, Ana |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Cunha, Ludmylla Costa Rodrigues, Susana Rosa Da Costa, Ana Faleiro, Maria Leonor Buttini, Francesca Grenha, Ana |
dc.subject.por.fl_str_mv |
Dry Powder Inhalers Alveolar Macrophages Aerodynamic Performance In-Vitro Delivery Rifabutin Rifampicin Polysaccharides Nanoparticles Microspheres |
topic |
Dry Powder Inhalers Alveolar Macrophages Aerodynamic Performance In-Vitro Delivery Rifabutin Rifampicin Polysaccharides Nanoparticles Microspheres |
description |
The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-07T14:53:25Z 2018-06 2018-06-01T00:00:00Z |
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/10400.1/11510 |
url |
http://hdl.handle.net/10400.1/11510 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2073-4360 10.3390/polym10060636 |
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 |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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 |
instname_str |
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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1799133264333504512 |