Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH

Detalhes bibliográficos
Autor(a) principal: Ferreira, Mariana Mendonca [UNIFESP]
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6344450
https://repositorio.unifesp.br/handle/11600/52823
Resumo: The interest in nanomaterials capable of acting in drug release processes has increased in the last decade specially the ones that involve drugs with administration restrictions. In this field, mesoporous silicas have been considered one of the most promising inorganic systems due to their unique chemical, structural and biological properties such as: chemical and structural stability in the physiological medium, high surface area, easy chemical modification, biocompatibility, biodegradability and low toxicity. In this study, mesoporous silica nanoparticles were coated with a chitosan layer in order to generate a hybrid nanoparticle capable of controlling the release of bioactive molecules by a process triggered by the acidification of the medium. Chitosan is a semi synthetic biopolymer, which due to its renewable origin and its processing in aqueous medium is considered sustainable, with interesting properties such as low toxicity, bactericidal activity, biocompatibility and biodegradability that are useful for biomedical applications. As the amino groups (pKa = 6.5) of the polymeric chain can be protonated in diluted acidic medium, at neutral or basic pH it is expected that the entanglement among the polymeric chains block the release of drugs previously immobilized into the silica pores. Whereas under acid pH, the protonation of these groups can promote conformational changes to the polymeric chains due to electrostatic repulsion that triggers the drug release. Different synthetic routes were evaluated in order to coat the mesoporous silica nanoparticles with chitosan by formation of covalent bonds between these moieties. The best result was achieved by coating the silica nanoparticles through the formation of imines bonds between amino groups present in a post-functionalized silica nanoparticle and in the chitosan promoted by glutaraldehyde, used as crosslinking agent. In this study, fluorescein was used as a model molecule for the evaluation of controlled release capabilities due to its optical properties that enable its easy spectrophotometric monitoring. The rate of release in acid medium was higher than in neutral or basic medium and the kinetics mechanism was dependent on the diffusion of the species through the pores. The produced hybrid nanoparticles presented sizes adequate to be captured by cells through endocytosis and showed drug release mechanism triggered by acidic pH which are required characteristics for their further use in intracellular release of bioactive species.
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spelling Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PHMesoporous silicaChitosanNanoparticleControlled releaseHybrid materialSílica mesoporosaQuitosanaNanopartículaLiberação controladaMaterial híbridoThe interest in nanomaterials capable of acting in drug release processes has increased in the last decade specially the ones that involve drugs with administration restrictions. In this field, mesoporous silicas have been considered one of the most promising inorganic systems due to their unique chemical, structural and biological properties such as: chemical and structural stability in the physiological medium, high surface area, easy chemical modification, biocompatibility, biodegradability and low toxicity. In this study, mesoporous silica nanoparticles were coated with a chitosan layer in order to generate a hybrid nanoparticle capable of controlling the release of bioactive molecules by a process triggered by the acidification of the medium. Chitosan is a semi synthetic biopolymer, which due to its renewable origin and its processing in aqueous medium is considered sustainable, with interesting properties such as low toxicity, bactericidal activity, biocompatibility and biodegradability that are useful for biomedical applications. As the amino groups (pKa = 6.5) of the polymeric chain can be protonated in diluted acidic medium, at neutral or basic pH it is expected that the entanglement among the polymeric chains block the release of drugs previously immobilized into the silica pores. Whereas under acid pH, the protonation of these groups can promote conformational changes to the polymeric chains due to electrostatic repulsion that triggers the drug release. Different synthetic routes were evaluated in order to coat the mesoporous silica nanoparticles with chitosan by formation of covalent bonds between these moieties. The best result was achieved by coating the silica nanoparticles through the formation of imines bonds between amino groups present in a post-functionalized silica nanoparticle and in the chitosan promoted by glutaraldehyde, used as crosslinking agent. In this study, fluorescein was used as a model molecule for the evaluation of controlled release capabilities due to its optical properties that enable its easy spectrophotometric monitoring. The rate of release in acid medium was higher than in neutral or basic medium and the kinetics mechanism was dependent on the diffusion of the species through the pores. The produced hybrid nanoparticles presented sizes adequate to be captured by cells through endocytosis and showed drug release mechanism triggered by acidic pH which are required characteristics for their further use in intracellular release of bioactive species.O interesse em nanomateriais capazes de atuarem em processos de liberação de fármacos que apresentam restrições quanto a forma de administração tem sido crescente na última década. Neste campo, as sílicas mesoporosas são consideradas como um dos sistemas inorgânicos promissores devido às suas propriedades químicas, estruturais e biológicas singulares como estabilidade química e estrutural no meio fisiológico, grande área superficial, fácil modificação química, biocompatibilidade, biodegradabilidade e baixa toxicidade. Neste estudo, nanopartículas de sílicas mesoporosas foram recobertas com uma camada de quitosana a fim de se gerar nanopartículas híbridas com capacidade de controlar a liberação de moléculas bioativas por um mecanismo desencadeado pela acidificação do meio. A quitosana, um biopolímero semissintético sustentável devido à sua origem renovável e seu processamento em meio aquoso, apresenta propriedades interessantes para uso biomédico como baixa toxicidade, atividade bactericida, biocompatibilidade e biodegradabilidade. Como os grupos amino (pKa = 6,5) presentes na cadeia polimérica podem ser protonados em meio ácido é esperado, que em pH neutro ou básico, o entrelaçamento entre as cadeias poliméricas bloqueie a liberação das espécies imobilizadas nos poros da sílica, enquanto em pH ácido, a protonação desses grupos provoque mudanças conformacionais geradas pela repulsão eletrostática entre as cadeias do biopolímero e desencadeie a liberação. Diferentes rotas sintéticas foram avaliadas com o intuito de imobilizar covalentemente a quitosana às nanopartículas de sílica. Os melhores resultados foram conseguidos promovendo o recobrimento das nanopartículas de sílica através da formação de ligação imina entre grupos aminos da nanopartícula funcionalizada e da cadeia da quitosana usando glutaraldeído como agente de formação de ligação cruzada. A fluoresceína foi usada como molécula modelo para a avaliação do processo de liberação controlada em razão de sua propriedades óticas que permitem seu fácil monitoramento espectrofotométrico. A cinética de liberação em meio ácido foi maior do que em meio neutro ou básico, sendo a velocidade de liberação dependente da difusão da espécie através dos poros. As nanopartículas híbridas produzidas apresentaram tamanhos adequados para serem capturadas pelas células por endocitose e liberação desencadeada por pH ácido, que são características necessárias para o seu posterior uso como vetores para liberação intracelular de espécies bioativasDados abertos - Sucupira - Teses e dissertações (2018)Universidade Federal de São PauloBizeto, Marcos Augusto [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Ferreira, Mariana Mendonca [UNIFESP]2020-03-25T12:10:34Z2020-03-25T12:10:34Z2018-04-27info:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/publishedVersion129 p.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6344450Dissertação - Mariana Mendonça Ferreira.pdfhttps://repositorio.unifesp.br/handle/11600/52823porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-10T14:33:55Zoai:repositorio.unifesp.br/:11600/52823Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-10T14:33:55Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
title Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
spellingShingle Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
Ferreira, Mariana Mendonca [UNIFESP]
Mesoporous silica
Chitosan
Nanoparticle
Controlled release
Hybrid material
Sílica mesoporosa
Quitosana
Nanopartícula
Liberação controlada
Material híbrido
title_short Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
title_full Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
title_fullStr Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
title_full_unstemmed Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
title_sort Nanopartículas de sílica mesoporosa recobertas com quitosana para liberação de moléculas bioativas controlada por PH
author Ferreira, Mariana Mendonca [UNIFESP]
author_facet Ferreira, Mariana Mendonca [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Bizeto, Marcos Augusto [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Ferreira, Mariana Mendonca [UNIFESP]
dc.subject.por.fl_str_mv Mesoporous silica
Chitosan
Nanoparticle
Controlled release
Hybrid material
Sílica mesoporosa
Quitosana
Nanopartícula
Liberação controlada
Material híbrido
topic Mesoporous silica
Chitosan
Nanoparticle
Controlled release
Hybrid material
Sílica mesoporosa
Quitosana
Nanopartícula
Liberação controlada
Material híbrido
description The interest in nanomaterials capable of acting in drug release processes has increased in the last decade specially the ones that involve drugs with administration restrictions. In this field, mesoporous silicas have been considered one of the most promising inorganic systems due to their unique chemical, structural and biological properties such as: chemical and structural stability in the physiological medium, high surface area, easy chemical modification, biocompatibility, biodegradability and low toxicity. In this study, mesoporous silica nanoparticles were coated with a chitosan layer in order to generate a hybrid nanoparticle capable of controlling the release of bioactive molecules by a process triggered by the acidification of the medium. Chitosan is a semi synthetic biopolymer, which due to its renewable origin and its processing in aqueous medium is considered sustainable, with interesting properties such as low toxicity, bactericidal activity, biocompatibility and biodegradability that are useful for biomedical applications. As the amino groups (pKa = 6.5) of the polymeric chain can be protonated in diluted acidic medium, at neutral or basic pH it is expected that the entanglement among the polymeric chains block the release of drugs previously immobilized into the silica pores. Whereas under acid pH, the protonation of these groups can promote conformational changes to the polymeric chains due to electrostatic repulsion that triggers the drug release. Different synthetic routes were evaluated in order to coat the mesoporous silica nanoparticles with chitosan by formation of covalent bonds between these moieties. The best result was achieved by coating the silica nanoparticles through the formation of imines bonds between amino groups present in a post-functionalized silica nanoparticle and in the chitosan promoted by glutaraldehyde, used as crosslinking agent. In this study, fluorescein was used as a model molecule for the evaluation of controlled release capabilities due to its optical properties that enable its easy spectrophotometric monitoring. The rate of release in acid medium was higher than in neutral or basic medium and the kinetics mechanism was dependent on the diffusion of the species through the pores. The produced hybrid nanoparticles presented sizes adequate to be captured by cells through endocytosis and showed drug release mechanism triggered by acidic pH which are required characteristics for their further use in intracellular release of bioactive species.
publishDate 2018
dc.date.none.fl_str_mv 2018-04-27
2020-03-25T12:10:34Z
2020-03-25T12:10:34Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6344450
Dissertação - Mariana Mendonça Ferreira.pdf
https://repositorio.unifesp.br/handle/11600/52823
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6344450
https://repositorio.unifesp.br/handle/11600/52823
identifier_str_mv Dissertação - Mariana Mendonça Ferreira.pdf
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 129 p.
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de São Paulo
publisher.none.fl_str_mv Universidade Federal de São Paulo
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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