Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica
Ano de defesa: | 2022 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/24587 |
Resumo: | The development of new nanocarriers for the so-called third-generation photosensitizers (FS) has contributed significantly to the evolution of photodynamic therapy (PDT). Due to its maximum absorption at wavelengths within the phototherapeutic window range (600-800 nm), low photochemical degradation, and adequate singlet oxygen quantum yield (ФΔ), magnesium phthalocyanine (MgPc) is considered a promising FS for use in PDT. However, its high hydrophobicity and formation of aggregates decrease its photodynamic activity in a physiological environment. Thus, the encapsulation of MgPc in nanostructures becomes necessary to improve its bioavailability and increase its phototherapeutic activity. From these considerations, the main objective of this work is to encapsulate MgPc in polymeric micelles obtained from block copolymers based on maltoheptaose (MH) and evaluate its photodynamic activity. By way of comparison, the encapsulation of MgPc in poly-ɛ-caprolactone (PCL) nanocapsules was also performed. The physicochemical characterization of the nanostructured systems (MH-b-PS@MgPc, MH-b-PMMA@MgPc, and PCL@MgPc) was carried out by determining the values of hydrodynamic diameter, polydipersion index, zeta potential, the total content of MgPc, encapsulation efficiency and physical stability over time by LUMiSizer. The photodynamic activity of the nanoparticles was evaluated by monitoring the photochemical degradation reaction of the chemical suppressor 1,3-diphenylisobenzofuran (DPBF). The kinetic profile of in vitro release of MgPc from the nanostructures and the toxicity and biodistribution of the nanocarriers against the nematodes Caenorhabditis elegans were also evaluated. The nanostructures presented nanometric sizes, low polydispersion indices (which confirm the homogeneity of the systems), negative zeta potential with high modulus values, and encapsulation efficiency above 95%. Analysis by LUMiSizer revealed that the polymeric micelles are highly stable in aqueous medium, with an estimated physical stability of three years. Evaluating the photodynamic activity of the nanoparticles it was concluded that polymeric micelles containing FS are capable of generating singlet oxygen at satisfactory levels for use in PDT, with Ф� values close to those of unencapsulated MgPc. The nanostructures present a sustained FS release profile, with biexponential model kinetics. The toxicity study showed that the nanoparticles cause a small reduction in the larval development of C. elegans, but do not induce lethality when the worms are exposed to low concentrations, and that they are mostly located in intestinal cells. Considering these results, it is concluded that nanostructured systems based on maltoheptaose are promising carriers for MgPc, with potential use in PDT. |
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2022-05-30T18:06:13Z2022-05-30T18:06:13Z2022-02-15http://repositorio.ufsm.br/handle/1/24587The development of new nanocarriers for the so-called third-generation photosensitizers (FS) has contributed significantly to the evolution of photodynamic therapy (PDT). Due to its maximum absorption at wavelengths within the phototherapeutic window range (600-800 nm), low photochemical degradation, and adequate singlet oxygen quantum yield (ФΔ), magnesium phthalocyanine (MgPc) is considered a promising FS for use in PDT. However, its high hydrophobicity and formation of aggregates decrease its photodynamic activity in a physiological environment. Thus, the encapsulation of MgPc in nanostructures becomes necessary to improve its bioavailability and increase its phototherapeutic activity. From these considerations, the main objective of this work is to encapsulate MgPc in polymeric micelles obtained from block copolymers based on maltoheptaose (MH) and evaluate its photodynamic activity. By way of comparison, the encapsulation of MgPc in poly-ɛ-caprolactone (PCL) nanocapsules was also performed. The physicochemical characterization of the nanostructured systems (MH-b-PS@MgPc, MH-b-PMMA@MgPc, and PCL@MgPc) was carried out by determining the values of hydrodynamic diameter, polydipersion index, zeta potential, the total content of MgPc, encapsulation efficiency and physical stability over time by LUMiSizer. The photodynamic activity of the nanoparticles was evaluated by monitoring the photochemical degradation reaction of the chemical suppressor 1,3-diphenylisobenzofuran (DPBF). The kinetic profile of in vitro release of MgPc from the nanostructures and the toxicity and biodistribution of the nanocarriers against the nematodes Caenorhabditis elegans were also evaluated. The nanostructures presented nanometric sizes, low polydispersion indices (which confirm the homogeneity of the systems), negative zeta potential with high modulus values, and encapsulation efficiency above 95%. Analysis by LUMiSizer revealed that the polymeric micelles are highly stable in aqueous medium, with an estimated physical stability of three years. Evaluating the photodynamic activity of the nanoparticles it was concluded that polymeric micelles containing FS are capable of generating singlet oxygen at satisfactory levels for use in PDT, with Ф� values close to those of unencapsulated MgPc. The nanostructures present a sustained FS release profile, with biexponential model kinetics. The toxicity study showed that the nanoparticles cause a small reduction in the larval development of C. elegans, but do not induce lethality when the worms are exposed to low concentrations, and that they are mostly located in intestinal cells. Considering these results, it is concluded that nanostructured systems based on maltoheptaose are promising carriers for MgPc, with potential use in PDT.O desenvolvimento de novos nanocarreadores para os chamados fotossensibilizadores (FS) de terceira geração vêm contribuindo significativamente para a evolução da terapia fotodinâmica (TFD). Por apresentar máxima absorção em comprimento de onda dentro do intervalo da janela fototerapêutica (600-800 nm), baixa degradação fotoquímica e adequado rendimento quântico de oxigênio singleto (Ф), a ftalocianina de magnésio (MgPc) é considerada um FS promissor para utilização em TFD. Entretanto, sua alta hidrofobicidade e a formação de agregados diminuem sua atividade fotodinâmica em meio fisiológico. Assim, a encapsulação da MgPc em nanoestruturas torna-se necessária, a afim de melhorar sua biodisponibilidade e aumentar a sua atividade fototerapêutica. A partir dessas considerações, o principal objetivo deste trabalho é encapsular a MgPc em micelas poliméricas obtidas a partir de copolímeros em bloco baseados em maltoheptaose (MH) e avaliar a sua atividade fotodinâmica. A título de comparação também foi realizada a encapsulação da MgPc em nanocápsulas de poli--caprolactona (PCL). A caracterização físico-química dos sistemas nanoestruturados (MH-b-PS@MgPc, MH-b-PMMA@MgPc e PCL@MgPc) foi realizada através da determinação dos valores de diâmetro hidrodinâmico, índice de polidipersão, potencial zeta, teor total de MgPc, eficiência de encapsulamento e estabilidade física ao longo do tempo utilizando o equipamento LUMiSizer. A atividade fotodinâmica das nanopartículas foi avaliada a partir do monitoramento da reação de degradação fotoquímica do supressor químico 1,3-difenilisobenzofurano (DPBF). Também foram avaliados o perfil cinético de liberação in vitro da MgPc a partir das nanoestruturas, e a toxicidade e biodistribuição dos nanocarreadores frente aos nematódeos Caenorhabditis elegans. As nanoestruturas apresentaram tamanhos nanométricos, baixos índices de polidispersão (que confirmam a homogeneidade dos sistemas), potencial zeta negativo com altos valores em módulo e eficiência de encapsulamento acima de 95%. A análise por LUMiSizer revelou que as micelas poliméricas são altamente estáveis em meio aquoso, com estabilidade física estimada em três anos. Avaliando a atividade fotodinâmica das nanopartículas, concluiu-se que as micelas poliméricas contendo FS são capazes de gerar oxigênio singleto em níveis satisfatórios para o emprego em TFD, com valores de Ф próximos aos da MgPc não encapsulada. As nanoestruturas apresentam perfil sustentado de liberação do FS, com cinética de modelo biexponencial. O estudo de toxicidade demonstrou que as nanopartículas causam uma pequena redução do desenvolvimento larval dos C. elegans, mas não induzem letalidade quando os vermes são expostos a baixas concentrações, e que as mesmas estão majoritariamente distribuídas em células intestinais. Considerando estes resultados conclui-se que os sistemas nanoestruturados baseados em maltoheptaose são carreadores promissores para a MgPc, com potencial emprego na TFD.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em QuímicaUFSMBrasilQuímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNanocarreadoresFtalocianina de magnésioCopolímeros em blocoMaltoheptaoseTerapia fotodinâmicaNanocarriersMagnesium phthalocyanineBlock coplymersMaltoheptaosePhotodynamic therapyCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAMicelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmicaMaltoheptaose-based block copolymer micelles containing magnesium phthalocyanine for application in photodynamic therapyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisVilletti, Marcos Antoniohttp://lattes.cnpq.br/8504489050993642Burgo, Thiago Augusto de Lima051bea13-9b6e-44dd-aa69-6bcfc48713d1600Silva, Leandro Barros daGarcia, Irene Teresinha SantosSilva, Cristiane de Bona dahttp://lattes.cnpq.br/6322763265178174Mattiazzi, Lia Mallmann100600000000600600600600600600606f8835-e936-4079-89b9-60e12681def441e481fd-d54d-473f-b652-1502473c6b9596f71632-1647-43b2-b523-60ec4d55bcf6b3bbf63b-d6e5-46da-87e7-954f4636334fc56fae84-29a4-4bd2-bfb3-82d8250be338reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGQUÍMICA_2022_MATTIAZZI_LIA.pdfDIS_PPGQUÍMICA_2022_MATTIAZZI_LIA.pdfDissertação de mestradoapplication/pdf3351167http://repositorio.ufsm.br/bitstream/1/24587/1/DIS_PPGQU%c3%8dMICA_2022_MATTIAZZI_LIA.pdf95c35e288c40ae9090021849e396fb9dMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
dc.title.alternative.eng.fl_str_mv |
Maltoheptaose-based block copolymer micelles containing magnesium phthalocyanine for application in photodynamic therapy |
title |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
spellingShingle |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica Mattiazzi, Lia Mallmann Nanocarreadores Ftalocianina de magnésio Copolímeros em bloco Maltoheptaose Terapia fotodinâmica Nanocarriers Magnesium phthalocyanine Block coplymers Maltoheptaose Photodynamic therapy CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
title_full |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
title_fullStr |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
title_full_unstemmed |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
title_sort |
Micelas de copolímeros em bloco à base de maltoheptaose contendo ftalocianina de magnésio para aplicação em terapia fotodinâmica |
author |
Mattiazzi, Lia Mallmann |
author_facet |
Mattiazzi, Lia Mallmann |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Villetti, Marcos Antonio |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8504489050993642 |
dc.contributor.advisor-co1.fl_str_mv |
Burgo, Thiago Augusto de Lima |
dc.contributor.advisor-co2.fl_str_mv |
Silva, Leandro Barros da |
dc.contributor.referee1.fl_str_mv |
Garcia, Irene Teresinha Santos |
dc.contributor.referee2.fl_str_mv |
Silva, Cristiane de Bona da |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6322763265178174 |
dc.contributor.author.fl_str_mv |
Mattiazzi, Lia Mallmann |
contributor_str_mv |
Villetti, Marcos Antonio Burgo, Thiago Augusto de Lima Silva, Leandro Barros da Garcia, Irene Teresinha Santos Silva, Cristiane de Bona da |
dc.subject.por.fl_str_mv |
Nanocarreadores Ftalocianina de magnésio Copolímeros em bloco Maltoheptaose Terapia fotodinâmica |
topic |
Nanocarreadores Ftalocianina de magnésio Copolímeros em bloco Maltoheptaose Terapia fotodinâmica Nanocarriers Magnesium phthalocyanine Block coplymers Maltoheptaose Photodynamic therapy CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Nanocarriers Magnesium phthalocyanine Block coplymers Maltoheptaose Photodynamic therapy |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
The development of new nanocarriers for the so-called third-generation photosensitizers (FS) has contributed significantly to the evolution of photodynamic therapy (PDT). Due to its maximum absorption at wavelengths within the phototherapeutic window range (600-800 nm), low photochemical degradation, and adequate singlet oxygen quantum yield (ФΔ), magnesium phthalocyanine (MgPc) is considered a promising FS for use in PDT. However, its high hydrophobicity and formation of aggregates decrease its photodynamic activity in a physiological environment. Thus, the encapsulation of MgPc in nanostructures becomes necessary to improve its bioavailability and increase its phototherapeutic activity. From these considerations, the main objective of this work is to encapsulate MgPc in polymeric micelles obtained from block copolymers based on maltoheptaose (MH) and evaluate its photodynamic activity. By way of comparison, the encapsulation of MgPc in poly-ɛ-caprolactone (PCL) nanocapsules was also performed. The physicochemical characterization of the nanostructured systems (MH-b-PS@MgPc, MH-b-PMMA@MgPc, and PCL@MgPc) was carried out by determining the values of hydrodynamic diameter, polydipersion index, zeta potential, the total content of MgPc, encapsulation efficiency and physical stability over time by LUMiSizer. The photodynamic activity of the nanoparticles was evaluated by monitoring the photochemical degradation reaction of the chemical suppressor 1,3-diphenylisobenzofuran (DPBF). The kinetic profile of in vitro release of MgPc from the nanostructures and the toxicity and biodistribution of the nanocarriers against the nematodes Caenorhabditis elegans were also evaluated. The nanostructures presented nanometric sizes, low polydispersion indices (which confirm the homogeneity of the systems), negative zeta potential with high modulus values, and encapsulation efficiency above 95%. Analysis by LUMiSizer revealed that the polymeric micelles are highly stable in aqueous medium, with an estimated physical stability of three years. Evaluating the photodynamic activity of the nanoparticles it was concluded that polymeric micelles containing FS are capable of generating singlet oxygen at satisfactory levels for use in PDT, with Ф� values close to those of unencapsulated MgPc. The nanostructures present a sustained FS release profile, with biexponential model kinetics. The toxicity study showed that the nanoparticles cause a small reduction in the larval development of C. elegans, but do not induce lethality when the worms are exposed to low concentrations, and that they are mostly located in intestinal cells. Considering these results, it is concluded that nanostructured systems based on maltoheptaose are promising carriers for MgPc, with potential use in PDT. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-05-30T18:06:13Z |
dc.date.available.fl_str_mv |
2022-05-30T18:06:13Z |
dc.date.issued.fl_str_mv |
2022-02-15 |
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://repositorio.ufsm.br/handle/1/24587 |
url |
http://repositorio.ufsm.br/handle/1/24587 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
100600000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Química |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
bitstream.url.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
|
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1794524402352652288 |