Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso 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/1/26240 |
Resumo: | New nanocarriers have been contributing to the development of so-called third-generation photosensitizers for use in photodynamic therapy (PDT). Chloro-aluminum phthalocyanine (ClAlPc) is a promising second-generation photosensitizer for use in PDT, that exhibits adequate singlet oxygen quantum yield (ΦΔ), strong absorption at the phototherapeutic window (600 - 800 nm) and low photodegradation. However, ClAlPc is characterized by highly hydrophobic, it’s resulting in a poor solubility in the physiological medium. To overcome this fact, the encapsulation of ClAlPc in nanocarriers is essential to promote a better bioavailability of the drug in the organism and consequently improve the phototherapeutic activity. Thus, the objective of this work was to encapsulate ClAlPc in MH-b-PMMA block copolymer nanocarriers (MH-b-PMMA@ClAlPc) and evaluate its photodynamic activity. As a comparison, this work also had the objective to encapsulate ClAlPc in poly-ε-caprolactone nanocapsules and in nanoemulsions of commercial surfactants (Span 60® and Tween 80® ). The physicochemical characterization of the nanoparticles was performed through hydrodynamic radius, polydipersion index, zeta potential, morphology, drug content, encapsulation efficiency and stability in accelerated conditions (LUMiSizer). In vitro evaluation of the photodynamic activity of the nanostructured systems was performed through a typical photodegradation experiment of the chemical quencher 1,3-diphenylbenzofuran (DPBF). The release kinetics profile of ClAlPc from the nanocarriers was also studied. The toxicity and biodistribution of nanoparticles were evaluated against the specie Caenorhabditis elegans. The nanostructured systems showed nanometer sizes, low polydispersity indices, negative zeta potential, with high values in modulus, what indicated a good stability, high encapsulation efficiency, nearly 100%. The analyses by LUMiSizer confirmed optimal stability for the MH-b-PMMA@ClAlPc nanoparticles, suggesting a shelf life of at least 3 years. Furthermore, the nanocarriers containing the photosensitizer were able to generate cytotoxic singlet oxygen species when irradiated with laser light (660 nm and power of 30 mW), showing ΦΔ values close to those of free ClAlPc. The nanoparticles showed a controlled and sustained release profile of the drug. In the toxicity study, the nanostructured systems induced a decrease in the larval development of C. elegans, however, at low concentrations, the nanoparticles did not induce nematode lethality. Furthermore, the biosdistribution analyses showed that the nanocarriers were localized mostly in the cells around the intestine, confirming the oral absorption of the nanoparticles. In conclusion, the nanocarriers prepared in this work are promising for carrying hydrophobic photosensitizers for use in PDT. |
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2022-09-22T20:34:19Z2022-09-22T20:34:19Z2022-08-09http://repositorio.ufsm.br/handle/1/26240New nanocarriers have been contributing to the development of so-called third-generation photosensitizers for use in photodynamic therapy (PDT). Chloro-aluminum phthalocyanine (ClAlPc) is a promising second-generation photosensitizer for use in PDT, that exhibits adequate singlet oxygen quantum yield (ΦΔ), strong absorption at the phototherapeutic window (600 - 800 nm) and low photodegradation. However, ClAlPc is characterized by highly hydrophobic, it’s resulting in a poor solubility in the physiological medium. To overcome this fact, the encapsulation of ClAlPc in nanocarriers is essential to promote a better bioavailability of the drug in the organism and consequently improve the phototherapeutic activity. Thus, the objective of this work was to encapsulate ClAlPc in MH-b-PMMA block copolymer nanocarriers (MH-b-PMMA@ClAlPc) and evaluate its photodynamic activity. As a comparison, this work also had the objective to encapsulate ClAlPc in poly-ε-caprolactone nanocapsules and in nanoemulsions of commercial surfactants (Span 60® and Tween 80® ). The physicochemical characterization of the nanoparticles was performed through hydrodynamic radius, polydipersion index, zeta potential, morphology, drug content, encapsulation efficiency and stability in accelerated conditions (LUMiSizer). In vitro evaluation of the photodynamic activity of the nanostructured systems was performed through a typical photodegradation experiment of the chemical quencher 1,3-diphenylbenzofuran (DPBF). The release kinetics profile of ClAlPc from the nanocarriers was also studied. The toxicity and biodistribution of nanoparticles were evaluated against the specie Caenorhabditis elegans. The nanostructured systems showed nanometer sizes, low polydispersity indices, negative zeta potential, with high values in modulus, what indicated a good stability, high encapsulation efficiency, nearly 100%. The analyses by LUMiSizer confirmed optimal stability for the MH-b-PMMA@ClAlPc nanoparticles, suggesting a shelf life of at least 3 years. Furthermore, the nanocarriers containing the photosensitizer were able to generate cytotoxic singlet oxygen species when irradiated with laser light (660 nm and power of 30 mW), showing ΦΔ values close to those of free ClAlPc. The nanoparticles showed a controlled and sustained release profile of the drug. In the toxicity study, the nanostructured systems induced a decrease in the larval development of C. elegans, however, at low concentrations, the nanoparticles did not induce nematode lethality. Furthermore, the biosdistribution analyses showed that the nanocarriers were localized mostly in the cells around the intestine, confirming the oral absorption of the nanoparticles. In conclusion, the nanocarriers prepared in this work are promising for carrying hydrophobic photosensitizers for use in PDT.Novos nanocarreadores vem contribuindo para o desenvolvimento dos chamados fotossensibilizadores de terceira geração visando o uso na terapia fotodinâmica (PDT). A ftalocianina de cloro-alumínio (ClAlPc) é um promissor fotossensibilizador de segunda geração para o emprego na PDT, pois apresenta rendimento quântico de oxigênio singleto (ΦΔ) adequado, absorção máxima no comprimento de onda janela fototerapêutica (600 - 800 nm) e baixa fotodegradação. Entretanto, a ClAlPc caracteriza-se por ser altamente hidrofóbica, resultando em uma baixa solubilidade em meios fisiológicos. Devido a este fato, a sua encapsulação em nanocarreadores é essencial para promover uma melhor biodisponibilidade do fármaco no organismo e consequentemente melhorar a sua atividade fototerapêutica. Sendo assim, o principal objetivo deste trabalho é encapsular a ClAlPc em nanocarreadores de copolímero em bloco MH-b-PMMA (MH-b-PMMA@ClAlPc) e avaliar a sua tividade fotodinâmica. A título de comparação, este trabalho também terá como objetivo encapsular a ClAlPc em nanocápsulas de poli-ε-caprolactona e em nanoemulsões de surfactantes comerciais (Span 60® e Tween 80® ). A caracterização físico-química das nanopartículas foi realizada através do raio hidrodinâmico, índice de polidipersão, potencial zeta, morfologia, conteúdo de fotossensibilizador, eficiência de encapsulamento e estabilidade em condições aceleradas (LUMiSizer). A avaliação in vitro da atividade fotodinâmica dos sistemas nanoestruturados foi realizada através de um típico experimento de fotodegradação do supressor químico 1,3-difenilbenzofurano (DPBF). Estudou-se também o perfil de cinética de liberação da ClAlPc contida nos nanocarreadores. A toxicidade e biodistribuição das nanopartículas foi avaliada frente à espécie Caenorhabditis elegans. Os sistemas nanoestruturados apresentaram tamanhos nanométricos, baixos índices de polidispersão e potencial zeta negativo, com altos valores em módulo, indicando uma boa estabilidade, alta eficiência de encapsulamento, próximo a 100%. As análises de LUMiSizer confirmaram uma ótima estabilidade para as nanopartículas MH-b-PMMA@ClAlPc, sugerindo um tempo de vida de prateleira de pelo menos 3 anos. Além disso, os nanocarreadores contendo o fotossensibilizador foram capazes de gerar espécies citotóxicas de oxigênio singleto quando irradiados com luz laser (660 nm e potência de 30 mW), apresentando valores de ΦΔ próximos ao da ClAlPc livre. As nanopartículas apresentaram um perfil de liberação controlado e sustentado da ClAlPc. No estudo de toxicidade, os sistemas nanoestruturados levaram a uma diminuição no comprimento do corpo dos nematódeos, entretanto, em baixas concentrações as nanopartículas não induziram o decréscimo na viabilidade celular. Além disso, as análises de biosdistribuição mostraram que os nanocarreadores se localizaram majoritariamente nas células ao redor do intestino, comprovando a absorção por via oral das nanopartículas. Sendo assim, conclui-se que os nanocarreadores preparados neste trabalho são promissores para o carreamento de fotossensibilizadores hidrofóbicos para emprego na PDT.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade 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 cloro-alumínioCopolímero maltoheptaose-b-polimetilmetacrilatoTerapia fotodinâmicaNanocarriersChloro-aluminum phthalocyanineMaltoheptaose-b-polymethylmethacrylate copolymerPhotodynamic therapyCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICANanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmicaNanoparticles of maltoheptaose-b-polymethylmethacrylate block copolymer containing chlorine-aluminium phalocianine for use in photodynamic therapyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisVilletti, Marcos Antoniohttp://lattes.cnpq.br/8504489050993642Iglesias, Bernardo AlmeidaBizzi, Cezar AugustoGarcia, Irene Teresinha Santoshttp://lattes.cnpq.br/2714397705794014Stefanello, Luiza Bertoldo100600000000600600600600600600606f8835-e936-4079-89b9-60e12681def48edf9767-e56c-4c49-ad3e-062a5f5be1d0fc9cad38-6b85-4a25-9108-19542c1775bebe6876cc-2db6-4d50-8c79-b4b0a2425b0ceac5d940-ee23-4a12-9898-34396e823d36reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
dc.title.alternative.eng.fl_str_mv |
Nanoparticles of maltoheptaose-b-polymethylmethacrylate block copolymer containing chlorine-aluminium phalocianine for use in photodynamic therapy |
title |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
spellingShingle |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica Stefanello, Luiza Bertoldo Nanocarreadores Ftalocianina de cloro-alumínio Copolímero maltoheptaose-b-polimetilmetacrilato Terapia fotodinâmica Nanocarriers Chloro-aluminum phthalocyanine Maltoheptaose-b-polymethylmethacrylate copolymer Photodynamic therapy CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
title_full |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
title_fullStr |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
title_full_unstemmed |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
title_sort |
Nanopartículas de copolímero em bloco de maltoheptaose-b-polimetilmetacrilato contendo ftalocianina de cloro-alumínio para o uso em terapia fotodinâmica |
author |
Stefanello, Luiza Bertoldo |
author_facet |
Stefanello, Luiza Bertoldo |
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 |
Iglesias, Bernardo Almeida |
dc.contributor.referee1.fl_str_mv |
Bizzi, Cezar Augusto |
dc.contributor.referee2.fl_str_mv |
Garcia, Irene Teresinha Santos |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2714397705794014 |
dc.contributor.author.fl_str_mv |
Stefanello, Luiza Bertoldo |
contributor_str_mv |
Villetti, Marcos Antonio Iglesias, Bernardo Almeida Bizzi, Cezar Augusto Garcia, Irene Teresinha Santos |
dc.subject.por.fl_str_mv |
Nanocarreadores Ftalocianina de cloro-alumínio Copolímero maltoheptaose-b-polimetilmetacrilato Terapia fotodinâmica |
topic |
Nanocarreadores Ftalocianina de cloro-alumínio Copolímero maltoheptaose-b-polimetilmetacrilato Terapia fotodinâmica Nanocarriers Chloro-aluminum phthalocyanine Maltoheptaose-b-polymethylmethacrylate copolymer Photodynamic therapy CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Nanocarriers Chloro-aluminum phthalocyanine Maltoheptaose-b-polymethylmethacrylate copolymer Photodynamic therapy |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
New nanocarriers have been contributing to the development of so-called third-generation photosensitizers for use in photodynamic therapy (PDT). Chloro-aluminum phthalocyanine (ClAlPc) is a promising second-generation photosensitizer for use in PDT, that exhibits adequate singlet oxygen quantum yield (ΦΔ), strong absorption at the phototherapeutic window (600 - 800 nm) and low photodegradation. However, ClAlPc is characterized by highly hydrophobic, it’s resulting in a poor solubility in the physiological medium. To overcome this fact, the encapsulation of ClAlPc in nanocarriers is essential to promote a better bioavailability of the drug in the organism and consequently improve the phototherapeutic activity. Thus, the objective of this work was to encapsulate ClAlPc in MH-b-PMMA block copolymer nanocarriers (MH-b-PMMA@ClAlPc) and evaluate its photodynamic activity. As a comparison, this work also had the objective to encapsulate ClAlPc in poly-ε-caprolactone nanocapsules and in nanoemulsions of commercial surfactants (Span 60® and Tween 80® ). The physicochemical characterization of the nanoparticles was performed through hydrodynamic radius, polydipersion index, zeta potential, morphology, drug content, encapsulation efficiency and stability in accelerated conditions (LUMiSizer). In vitro evaluation of the photodynamic activity of the nanostructured systems was performed through a typical photodegradation experiment of the chemical quencher 1,3-diphenylbenzofuran (DPBF). The release kinetics profile of ClAlPc from the nanocarriers was also studied. The toxicity and biodistribution of nanoparticles were evaluated against the specie Caenorhabditis elegans. The nanostructured systems showed nanometer sizes, low polydispersity indices, negative zeta potential, with high values in modulus, what indicated a good stability, high encapsulation efficiency, nearly 100%. The analyses by LUMiSizer confirmed optimal stability for the MH-b-PMMA@ClAlPc nanoparticles, suggesting a shelf life of at least 3 years. Furthermore, the nanocarriers containing the photosensitizer were able to generate cytotoxic singlet oxygen species when irradiated with laser light (660 nm and power of 30 mW), showing ΦΔ values close to those of free ClAlPc. The nanoparticles showed a controlled and sustained release profile of the drug. In the toxicity study, the nanostructured systems induced a decrease in the larval development of C. elegans, however, at low concentrations, the nanoparticles did not induce nematode lethality. Furthermore, the biosdistribution analyses showed that the nanocarriers were localized mostly in the cells around the intestine, confirming the oral absorption of the nanoparticles. In conclusion, the nanocarriers prepared in this work are promising for carrying hydrophobic photosensitizers for use in PDT. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-09-22T20:34:19Z |
dc.date.available.fl_str_mv |
2022-09-22T20:34:19Z |
dc.date.issued.fl_str_mv |
2022-08-09 |
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/1/26240 |
url |
http://repositorio.ufsm.br/handle/1/26240 |
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 |
606f8835-e936-4079-89b9-60e12681def4 8edf9767-e56c-4c49-ad3e-062a5f5be1d0 fc9cad38-6b85-4a25-9108-19542c1775be be6876cc-2db6-4d50-8c79-b4b0a2425b0c eac5d940-ee23-4a12-9898-34396e823d36 |
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 |
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Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
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UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
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http://repositorio.ufsm.br/bitstream/1/26240/2/license_rdf http://repositorio.ufsm.br/bitstream/1/26240/3/license.txt http://repositorio.ufsm.br/bitstream/1/26240/1/DIS_PPGQU%c3%8dMICA_2022_STEFANELLO_LUIZA.pdf |
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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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1794524467715637248 |