Formulation of galactomannan microparticles as insulin carriers

Detalhes bibliográficos
Autor(a) principal: Galrinho, Miguel Feijão
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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spelling 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
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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
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