Therapeutic deep eutectic systems as promising new tools in the anticancer battle
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/10362/132853 |
Resumo: | Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with NSAIDs, like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES therapeutic potential activity, their physico-chemical properties, bioavailability and bioactivity, were explored using an integrative approach to determine their anti-CRC activity. Our results show that Safranal:Ibuprofen (3:1), Safranal:Ibuprofen (4:1) and Menthol:Ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. Menthol:Ibuprofen (3:1) anti proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of ROS production, and induction of apoptosis via caspase-3. On the other hand, Safranal:Ibuprofen (3:1) and Safranal:Ibuprofen (4:1) seem to prevent tumour cells expansion only through the induction of apoptosis via caspase-3. These systems also present an increasement in Ibuprofen permeability, with Menthol:Ibuprofen (3:1) increasing also Ibuprofen solubility and the overall bioavailability. |
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Therapeutic deep eutectic systems as promising new tools in the anticancer battleColorectal cancerDeep eutectic systemsTHEDESNSAIDNatural compoundsTerpenesDomínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e TecnologiasCancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with NSAIDs, like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES therapeutic potential activity, their physico-chemical properties, bioavailability and bioactivity, were explored using an integrative approach to determine their anti-CRC activity. Our results show that Safranal:Ibuprofen (3:1), Safranal:Ibuprofen (4:1) and Menthol:Ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. Menthol:Ibuprofen (3:1) anti proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of ROS production, and induction of apoptosis via caspase-3. On the other hand, Safranal:Ibuprofen (3:1) and Safranal:Ibuprofen (4:1) seem to prevent tumour cells expansion only through the induction of apoptosis via caspase-3. These systems also present an increasement in Ibuprofen permeability, with Menthol:Ibuprofen (3:1) increasing also Ibuprofen solubility and the overall bioavailability.O cancro continua a ser um dos maiores problemas de saúde em todo o mundo, sendo que o cancro colorretal é o terceiro mais incidente e o segundo mais letal. A inflamação está altamente associada ao desenvolvimento e persistência do cancro, por esse motivo, a redução do microambiente inflamatório representa uma estratégia terapêutica promissora. Sistemas eutéticos, em inglês, Deep eutectic systems (DES) são sistemas baseados na combinação de diferentes componentes que em conjunto e a um determinado rácio molar apresentam uma grande diminuição do ponto de fusão em comparação com os compostos individuais. Quando um dos componentes do DES é um ingrediente farmacêutico ativo ele é designado de sistemas eutéticos terapêuticos, therapeutic deep eutectic system (THEDES). Novos THEDES a conjugar terpenos com propriedades anticancerígenas, como mentol, safranal e linalool, com anti-inflamatórios não esteroides, como ibuprofeno, cetoprofen e flurbiprofeno. Para avaliar o potencial terapêutico dos THEDES, as suas propriedades físico- -químicas, biodisponibilidade e bioatividade foram exploradas ao longo da tese como uma análise integrativa para determinar as suas atividades contra o cancro colorretal. Os nossos resultados demonstram que o Safranal:Ibuprofeno (3:1), Safranal:Ibuprofeno (4:1) e Mentol:Ibuprofeno (3:1) apresentam uma atividade terapêutica promissora contra as células do cancro colorretal devido a uma ação citotóxica seletiva contra as células cancerígenas. A ação do Mentol:Ibuprofeno (3:1) como anti-proliferativo contra as células cancerígenas aparenta estar relacionada com a disrupção da membrana celular, redução da inflamação através da redução da produção de ROS, e através da indução da apoptose via caspase-3. Por outro lado, Safranal:Ibuprofeno (3:1) e Safranal:Ibuprofeno (4:1) aparentam prevenir a expansão das células tumorais apenas através da indução da apoptose via caspase-3. Adicionalmente, estes sistemas também apresentam um aumento da permeabilidade do Ibuprofeno, com o sistema Mentol:Ibuprofeno (3:1) aumentando também a solubilidade do Ibuprofeno e a sua biodisponibilidade no geral.Duarte, AnaRUNPereira, Joana Félix2022-02-14T15:59:22Z2022-012022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/132853enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:11:31Zoai:run.unl.pt:10362/132853Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:47:36.923183Repositório 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 |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
title |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
spellingShingle |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle Pereira, Joana Félix Colorectal cancer Deep eutectic systems THEDES NSAID Natural compounds Terpenes Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
title_short |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
title_full |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
title_fullStr |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
title_full_unstemmed |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
title_sort |
Therapeutic deep eutectic systems as promising new tools in the anticancer battle |
author |
Pereira, Joana Félix |
author_facet |
Pereira, Joana Félix |
author_role |
author |
dc.contributor.none.fl_str_mv |
Duarte, Ana RUN |
dc.contributor.author.fl_str_mv |
Pereira, Joana Félix |
dc.subject.por.fl_str_mv |
Colorectal cancer Deep eutectic systems THEDES NSAID Natural compounds Terpenes Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
topic |
Colorectal cancer Deep eutectic systems THEDES NSAID Natural compounds Terpenes Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
description |
Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with NSAIDs, like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES therapeutic potential activity, their physico-chemical properties, bioavailability and bioactivity, were explored using an integrative approach to determine their anti-CRC activity. Our results show that Safranal:Ibuprofen (3:1), Safranal:Ibuprofen (4:1) and Menthol:Ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. Menthol:Ibuprofen (3:1) anti proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of ROS production, and induction of apoptosis via caspase-3. On the other hand, Safranal:Ibuprofen (3:1) and Safranal:Ibuprofen (4:1) seem to prevent tumour cells expansion only through the induction of apoptosis via caspase-3. These systems also present an increasement in Ibuprofen permeability, with Menthol:Ibuprofen (3:1) increasing also Ibuprofen solubility and the overall bioavailability. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-02-14T15:59:22Z 2022-01 2022-01-01T00:00:00Z |
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 |
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http://hdl.handle.net/10362/132853 |
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http://hdl.handle.net/10362/132853 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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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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