Formulation of galactomannan microparticles as insulin carriers
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/35099 |
Resumo: | Insulin is a protein hormone responsible for various functions at the metabolic level. The deficiency of this hormone is compensated by subcutaneous administration which can bring discomfort. The pulmonary pathway shows potential as an alternative route, using microparticles as transporters. Galactomannans are polysaccharides with potential to be used as base material for microparticles preparation. In this work, locust bean gum (LBG) was used as a source of galactomannans. However, the high viscosity can bring some problems to the microparticle preparation. To reduce the viscosity, it was performed a microwave treatment (MW). Depolymerized LBG was fractionated by ultrafiltration allowing to obtain fractions of molecular weight >300 kDa (R300), 300-100 kDa (R100), 100-50 kDa (R50), 50-30 kDa (R30), 30-10 (R10) and <10 kDa (P10). Mannose and galactose were the main sugars identified in all samples, in agreement with the galactomannan composition. The ratio mannose:galactose varied between 3.3 and 4.0 showing that the branching degree was maintained. Insulin was added in a 1:10 (insulin:galactomannan, w/w) ratio to each fraction produced and spray-dried, forming particles. By scanning electron microscopy (SEM), “raisin-like” structures were observed in all samples with a variation on size distribution that allowed the denomination of microparticles. Fractions of higher molecular weight led to microparticles of 1-5 μm, considered to be within the respirable range, while the fraction of low molecular weight (30-10 kDa) led to microparticles with 92% in a 5-15 μm range, out of the required values for pulmonary delivery. Total insulin release occurred along 40 min in a linear way. The microparticles with 30-10 kDa material had a faster release, in only 20 min. The combination of MW, ultrafiltration and spray-drying techniques show potential for microparticle preparation for pulmonary delivery of insulin, where the speed of release can be controlled by the galactomannan dimensions. |
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Formulation of galactomannan microparticles as insulin carriersMicroparticlesLBGSpray-dryingInsulinPulmonary administrationInsulin is a protein hormone responsible for various functions at the metabolic level. The deficiency of this hormone is compensated by subcutaneous administration which can bring discomfort. The pulmonary pathway shows potential as an alternative route, using microparticles as transporters. Galactomannans are polysaccharides with potential to be used as base material for microparticles preparation. In this work, locust bean gum (LBG) was used as a source of galactomannans. However, the high viscosity can bring some problems to the microparticle preparation. To reduce the viscosity, it was performed a microwave treatment (MW). Depolymerized LBG was fractionated by ultrafiltration allowing to obtain fractions of molecular weight >300 kDa (R300), 300-100 kDa (R100), 100-50 kDa (R50), 50-30 kDa (R30), 30-10 (R10) and <10 kDa (P10). Mannose and galactose were the main sugars identified in all samples, in agreement with the galactomannan composition. The ratio mannose:galactose varied between 3.3 and 4.0 showing that the branching degree was maintained. Insulin was added in a 1:10 (insulin:galactomannan, w/w) ratio to each fraction produced and spray-dried, forming particles. By scanning electron microscopy (SEM), “raisin-like” structures were observed in all samples with a variation on size distribution that allowed the denomination of microparticles. Fractions of higher molecular weight led to microparticles of 1-5 μm, considered to be within the respirable range, while the fraction of low molecular weight (30-10 kDa) led to microparticles with 92% in a 5-15 μm range, out of the required values for pulmonary delivery. Total insulin release occurred along 40 min in a linear way. The microparticles with 30-10 kDa material had a faster release, in only 20 min. The combination of MW, ultrafiltration and spray-drying techniques show potential for microparticle preparation for pulmonary delivery of insulin, where the speed of release can be controlled by the galactomannan dimensions.A insulina é uma hormona proteica, responsável por várias funções ao nível metabólico. A sua deficiência é compensada pela administração subcutânea, que gera desconforto. A via pulmonar demonstra potencial como rota alternativa, usando micropartículas como transportadores de insulina. As galactomananas são polissacarídeos com potencial para serem utilizadas como material de base para a preparação de micropartículas. Neste trabalho, a goma de alfarroba (LBG) foi usada como fonte de galactomananas. No entanto, a sua elevada viscosidade acarreta problemas na preparação de micropartículas. De forma a reduzir a viscosidade da LBG, foi realizado um tratamento por micro-ondas (MW). A LBG despolimerizada foi posteriormente fracionada através de ultrafiltração, obtendo uma fração de peso molecular >300 kDa (R300), de 300-100 kDa (R100), 100-50 kDa (R50), 50-30 kDa (R30), 30-10 kDa (R10) e inferior a 10 kDa (P10). R300 e P10 foram as frações mais abundantes. A manose e a galactose foram os principais açucares identificados em todas as amostras de acordo com a composição em galactomananas. O rácio manose:galactose variou entre 3,3 e 4,0, evidenciando a manutenção do grau de ramificação. A insulina foi adicionada numa proporção de 1:10 (insulina:galactomanana, m/m) a cada uma das frações produzidas e atomizadas, formando partículas. Através da microscopia eletrónica de varrimento (SEM) foram observadas estruturas semelhantes a “uva-passa” em todas as amostras com uma variação na distribuição de dimensões que permite a denominação de micropartículas. A utilização das frações de pesos moleculares mais elevados conduziu a micropartículas de 1-5 μm, consideradas dentro da gama respirável, enquanto a fração de menor peso (30-10 kDa) formou micropartículas em que 92% tinham dimensões entre 5-15 μm, fora da gama requerida para administração pulmonar. A libertação da insulina decorreu de forma linear até à totalidade no prazo de 40 min, exceto para as micropartículas com material de 30-10 kDa onde a libertação ocorreu em apenas 20 min. A combinação das técnicas de MW, ultrafiltração, e atomização, demonstram potencial para preparar micropartículas para administração pulmonar de insulina, em que a velocidade de libertação da mesma pode ser controlada pela dimensão da galactomanana.2023-07-24T00:00:00Z2022-07-18T00:00:00Z2022-07-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/35099engGalrinho, Miguel Feijãoinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:07:33Zoai:ria.ua.pt:10773/35099Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:06:11.605946Repositório 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 |
Formulation of galactomannan microparticles as insulin carriers |
title |
Formulation of galactomannan microparticles as insulin carriers |
spellingShingle |
Formulation of galactomannan microparticles as insulin carriers Galrinho, Miguel Feijão Microparticles LBG Spray-drying Insulin Pulmonary administration |
title_short |
Formulation of galactomannan microparticles as insulin carriers |
title_full |
Formulation of galactomannan microparticles as insulin carriers |
title_fullStr |
Formulation of galactomannan microparticles as insulin carriers |
title_full_unstemmed |
Formulation of galactomannan microparticles as insulin carriers |
title_sort |
Formulation of galactomannan microparticles as insulin carriers |
author |
Galrinho, Miguel Feijão |
author_facet |
Galrinho, Miguel Feijão |
author_role |
author |
dc.contributor.author.fl_str_mv |
Galrinho, Miguel Feijão |
dc.subject.por.fl_str_mv |
Microparticles LBG Spray-drying Insulin Pulmonary administration |
topic |
Microparticles LBG Spray-drying Insulin Pulmonary administration |
description |
Insulin is a protein hormone responsible for various functions at the metabolic level. The deficiency of this hormone is compensated by subcutaneous administration which can bring discomfort. The pulmonary pathway shows potential as an alternative route, using microparticles as transporters. Galactomannans are polysaccharides with potential to be used as base material for microparticles preparation. In this work, locust bean gum (LBG) was used as a source of galactomannans. However, the high viscosity can bring some problems to the microparticle preparation. To reduce the viscosity, it was performed a microwave treatment (MW). Depolymerized LBG was fractionated by ultrafiltration allowing to obtain fractions of molecular weight >300 kDa (R300), 300-100 kDa (R100), 100-50 kDa (R50), 50-30 kDa (R30), 30-10 (R10) and <10 kDa (P10). Mannose and galactose were the main sugars identified in all samples, in agreement with the galactomannan composition. The ratio mannose:galactose varied between 3.3 and 4.0 showing that the branching degree was maintained. Insulin was added in a 1:10 (insulin:galactomannan, w/w) ratio to each fraction produced and spray-dried, forming particles. By scanning electron microscopy (SEM), “raisin-like” structures were observed in all samples with a variation on size distribution that allowed the denomination of microparticles. Fractions of higher molecular weight led to microparticles of 1-5 μm, considered to be within the respirable range, while the fraction of low molecular weight (30-10 kDa) led to microparticles with 92% in a 5-15 μm range, out of the required values for pulmonary delivery. Total insulin release occurred along 40 min in a linear way. The microparticles with 30-10 kDa material had a faster release, in only 20 min. The combination of MW, ultrafiltration and spray-drying techniques show potential for microparticle preparation for pulmonary delivery of insulin, where the speed of release can be controlled by the galactomannan dimensions. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-07-18T00:00:00Z 2022-07-18 2023-07-24T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/35099 |
url |
http://hdl.handle.net/10773/35099 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
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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 |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137716631240704 |