Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs

Detalhes bibliográficos
Autor(a) principal: Guerreiro, Filipa Raquel Horta
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/7715
Resumo: Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015
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spelling Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugsCiências biomédicasTuberculose pulmonarTratamentoResistênciaTransportadoresMicropartículasPolímerosDomínio/Área Científica::Ciências Médicas::Ciências da SaúdeDissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015Microparticles (MPs) of konjac glucomannan (KGM) are proposed in this thesis as an alternative therapeutic approach for antitubercular drug delivery to the lung, in the ambit of tuberculosis (TB) therapy. KGM is composed of mannose groups that might comprise an entry mechanism in macrophages infected with Mycobacterium tuberculosis, mimicking one of the input paths of this infectious agent causer of TB. For this purpose, KGM MPs need to have certain properties, in particular an aerodynamic diameter between 1 and 3 μm that enables reaching the alveolar zone. These properties might be attained by a production using spray-drying technology. The objective of this work was to produce MPs of KGM through this process and associate two first-line antitubercular drugs, isoniazid (INH) and rifabutin (RFB). Furthermore, the effect of incorporating mannitol or leucine in the microparticle formulations was evaluated, regarding MPs aerodynamic characteristics, drug association and release, and biocompatibility profile. After an initial optimization that required a hydrolysis of the original KGM polymer to enable spray-drying, several formulations of MPs were produced and characterised. The use of mannitol or leucine has demonstrated to improve the flow properties of some formulations, as did the association of RFB. However, the incorporation of excipients brought some disadvantages, especially regarding the in vitro release rate of the drug, which became faster. Additionally, the incorporation of mannitol was found to affect the association of INH, which became lower, suggesting a competing effect between INH and mannitol. Cytotoxicity assays in alveolar epithelial cells revealed that RFB-loaded KGM MPs may have a considerably toxic effect when used at a concentration of 1 mg/mL, in particular if MPs are also comprised of leucine. The obtained results indicate that KGM MPs are suitable inhalable delivery systems for antitubercular drugs. Considering that a combination of drugs is advised by WHO in TB treatment, no benefit was found to occur from the incorporation of either leucine or mannitol in the formulation of KGM MPs.Grenha, AnaSapientiaGuerreiro, Filipa Raquel Horta2017-02-19T01:30:09Z2015-12-1620152015-12-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.1/7715TID:201177927enginfo: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:RCAAP2023-07-24T10:18:52Zoai:sapientia.ualg.pt:10400.1/7715Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:00:01.328802Repositório 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 Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
title Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
spellingShingle Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
Guerreiro, Filipa Raquel Horta
Ciências biomédicas
Tuberculose pulmonar
Tratamento
Resistência
Transportadores
Micropartículas
Polímeros
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
title_short Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
title_full Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
title_fullStr Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
title_full_unstemmed Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
title_sort Spray-dried polysaccharide microparticles aimed at pulmonary delivery of antitubercular drugs
author Guerreiro, Filipa Raquel Horta
author_facet Guerreiro, Filipa Raquel Horta
author_role author
dc.contributor.none.fl_str_mv Grenha, Ana
Sapientia
dc.contributor.author.fl_str_mv Guerreiro, Filipa Raquel Horta
dc.subject.por.fl_str_mv Ciências biomédicas
Tuberculose pulmonar
Tratamento
Resistência
Transportadores
Micropartículas
Polímeros
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
topic Ciências biomédicas
Tuberculose pulmonar
Tratamento
Resistência
Transportadores
Micropartículas
Polímeros
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
description Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015
publishDate 2015
dc.date.none.fl_str_mv 2015-12-16
2015
2015-12-16T00:00:00Z
2017-02-19T01:30:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/7715
TID:201177927
url http://hdl.handle.net/10400.1/7715
identifier_str_mv TID:201177927
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.format.none.fl_str_mv application/pdf
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
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