POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4)
Ano de defesa: | 2021 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso embargado |
Idioma: | por |
Instituição de defesa: |
Universidade Franciscana
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Nanociências
|
Departamento: |
Biociências e Nanomateriais
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/998 |
Resumo: | Acute promyelocytic leukemia is highlighted by the fusion of the PML-RARA genes causing cellular immaturity and accelerated proliferation of promyelocytes, causing symptoms such as hemorrhagic crises. Despite the efficacy of drugs such as all-trans retinoic acid and arsenic trioxide, some patients have important adverse reactions. Studies indicate that natural products are capable of acting in a chemotherapeutic manner with no or low adverse effect. In this context, cocoa (Theobroma cacao L.) was investigated for containing a chemical matrix rich in polyphenols and methylxanthines, capable of acting in an anti-tumor, anti- inflammatory and antioxidant manner. Due to its low bioavailability, an outbreak of nanotechnology as an efficient alternative to provide and improve the solubility of compounds through liposomal nanocarriers. The present study aims to evaluate the potential antitumor effect of liposomes containing cocoa against acute promyelocytic leukemia cells. Liposomes containing cocoa powder were collected in procedures of 1, 2 and 3 mg / mL-1 by the reverse phase evaporation method. The formulations produced were stored at room temperature (RT) (24 ± 2 ºC), refrigeration (RE) (4 ± 2 ºC) and climatic chamber (CC) (40 ºC 75% relative humidity) for evaluation during 90-day stability. Average particle diameter, polydispersity index, pH, catechin and methylxanthine content, encapsulation efficiency and organoleptic characteristics were adopted. Subsequently, a possible cytotoxic effect of liposomes and free cocoa was evaluated on fibroblast cell line (HFF-1) and acute promyelocytic leukemia (NB-4) from cell viability and levels of reactive oxygen species. Liposomes containing 1 mg / mL- 'remained stable for 30 days when stored in refrigeration, particle volume of 216.8 nm, polydispersity index of 0.375, zeta potential of -7.27 mV, pH 5.55 and content 3.23% theobromine, 0.74% theophylline, 1.11% catechin, 1.59% caffeine. In in vitro tests, the HFF-1 strain did not show reduced cell viability and proliferation in a reduced way. Still, it was found that the NB-4 cells dissipated cell proliferation and increased levels of reactive oxygen species within 72 hours in both treatments. It is concluded that liposomes are promising nanostructures for the encapsulation of catechins and methylxanthines as the compounds present in cocoa, in addition to having a potential carginogenic effect in acute promyelocytic leukemia cells. |
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Gomes, PatríciaCadoná, FrancineBagatini, Margarete DulceSilva, William Leonardo daRibeiro, Mariana Fernandes2021-06-30T14:15:28Z2022-05-222021-03-26Ribeiro, Mariana Fernandes. POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4). 2021. 69f. Dissertação( Programa de Pós-Graduação em Nanociências) - Universidade Franciscana, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/998Acute promyelocytic leukemia is highlighted by the fusion of the PML-RARA genes causing cellular immaturity and accelerated proliferation of promyelocytes, causing symptoms such as hemorrhagic crises. Despite the efficacy of drugs such as all-trans retinoic acid and arsenic trioxide, some patients have important adverse reactions. Studies indicate that natural products are capable of acting in a chemotherapeutic manner with no or low adverse effect. In this context, cocoa (Theobroma cacao L.) was investigated for containing a chemical matrix rich in polyphenols and methylxanthines, capable of acting in an anti-tumor, anti- inflammatory and antioxidant manner. Due to its low bioavailability, an outbreak of nanotechnology as an efficient alternative to provide and improve the solubility of compounds through liposomal nanocarriers. The present study aims to evaluate the potential antitumor effect of liposomes containing cocoa against acute promyelocytic leukemia cells. Liposomes containing cocoa powder were collected in procedures of 1, 2 and 3 mg / mL-1 by the reverse phase evaporation method. The formulations produced were stored at room temperature (RT) (24 ± 2 ºC), refrigeration (RE) (4 ± 2 ºC) and climatic chamber (CC) (40 ºC 75% relative humidity) for evaluation during 90-day stability. Average particle diameter, polydispersity index, pH, catechin and methylxanthine content, encapsulation efficiency and organoleptic characteristics were adopted. Subsequently, a possible cytotoxic effect of liposomes and free cocoa was evaluated on fibroblast cell line (HFF-1) and acute promyelocytic leukemia (NB-4) from cell viability and levels of reactive oxygen species. Liposomes containing 1 mg / mL- 'remained stable for 30 days when stored in refrigeration, particle volume of 216.8 nm, polydispersity index of 0.375, zeta potential of -7.27 mV, pH 5.55 and content 3.23% theobromine, 0.74% theophylline, 1.11% catechin, 1.59% caffeine. In in vitro tests, the HFF-1 strain did not show reduced cell viability and proliferation in a reduced way. Still, it was found that the NB-4 cells dissipated cell proliferation and increased levels of reactive oxygen species within 72 hours in both treatments. It is concluded that liposomes are promising nanostructures for the encapsulation of catechins and methylxanthines as the compounds present in cocoa, in addition to having a potential carginogenic effect in acute promyelocytic leukemia cells.A leucemia promielocítica aguda caracteriza-se pela fusão dos genes PML-RARA causando a imaturidade celular e proliferação acelerada dos promielócitos, causando sintomas como crises hemorrágicas. Apesar da eficácia de fármacos como ácido all-trans retinóico e trióxido de arsênio, parte dos pacientes apresentam reações adversas importantes. Estudos apontam que produtos naurais são capazes de atuar de maneira quimioterápica com efeito adverso baixo ou nulo. Nesse contexto, o cacau (Theobroma cacao L.) tem sido investigado por conter uma matriz química rica em polifenóis e metilxantinas, capazes de atuar de forma antitumoral, anti-inflamatória e antioxidante. Devido a sua baixa biodisponibilidade, a nanotecnologia surge como uma alternativa eficiente para preservar e melhorar a solubilidade de compostos através dos nanocarreadores lipossomicos. O presente trabalho tem com objetivo avaliar o potencial efeito antitumoral de lipossomas contendo cacau frente a células de leucemia promielocítica aguda. Foram produzidos lipossomas contendo cacau em pó nas concentrações de 1, 2 e 3 mg/ mL-1 pelo método de evaporação em fase reversa. As formulações produzidas foram armazenadas em temperatura ambiente (TA) (24 ± 2 ºC), refrigeração (RE) (4 ± 2 ºC) e câmara climática (CC) (40 ºC 75% de umidade relativa) para avaliação da estabilidade durante 90 dias. Foram avaliados o diâmetro médio de partícula, índice de polidispersão, pH, teor de catequinas e metilxantinas, eficiência de encapsulação e características organolépticas. Posteriormente foi avaliado um possível efeito citotóxico dos lipossomas e cacau livre em linhagem celular de fibroblastos (HFF-1) e leuceimia promielocitica aguda (NB-4) a partir da viabilidade celular e níveis de espécies reativas de oxigênio. Os lipossomas contendo 1 mg/ mL-‘ se mantiveram estaveis durante 30 dias quando armazenados em refrigeração, apresentando diâmetro de partícula de 216,8 nm, índice de polidispersão de 0,375, potencial zeta de -7,27 mV, pH 5,55 e teor de teobromina de 3,23%, teofilina 0,74%, catequina 1,11%, cafeína 1,59%. Nos testes in vitro, a linhagem HFF-1 não apresentou diminuição da viabilidade e proliferação celular de forma significativa. Ainda, verificou-se que as células NB-4 apresentaram diminuição de proliferação celular e aumento dos níveis de espécies reativas de oxigênio no período de 72 horas em ambos os tratamentos. Conclui-se que os lipossomas são nanoestruturas promissoras para o encapsulamento de catequinas e metilxantinas como os compostos presentes no cacau, além de ter um potencial efeito carginogênico em células de leucemia promielocítica aguda.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2021-06-30T14:15:28Z No. of bitstreams: 3 DissertacaoMarianaFernandesRibeiro_VersaoParcial.pdf: 1054305 bytes, checksum: f8fd716b41f063e75e24634d9bd1ea1a (MD5) Dissertacao_MarianaFernandesRibeiro_SemAssinaturas.pdf: 2245012 bytes, checksum: b0074752d77d0ea32a8f58b99e0ecbc4 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2021-06-30T14:15:28Z (GMT). No. of bitstreams: 3 DissertacaoMarianaFernandesRibeiro_VersaoParcial.pdf: 1054305 bytes, checksum: f8fd716b41f063e75e24634d9bd1ea1a (MD5) Dissertacao_MarianaFernandesRibeiro_SemAssinaturas.pdf: 2245012 bytes, checksum: b0074752d77d0ea32a8f58b99e0ecbc4 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2021-03-26application/pdfhttp://www.tede.universidadefranciscana.edu.br:8080/retrieve/8147/Dissertacao_MarianaFernandesRibeiro_SemAssinaturas.pdf.jpghttp://www.tede.universidadefranciscana.edu.br:8080/retrieve/8158/DissertacaoMarianaFernandesRibeiro_VersaoParcial.pdf.jpgporUniversidade FranciscanaPrograma de Pós-Graduação em NanociênciasUFNBrasilBiociências e Nanomateriaishttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/embargoedAccessCacau, Câncer, Nanotecnologia, PML-RARA, Polifenóis.Cocoa, Cancer, Nanotechnology, PML RARA, PolyphenolsNanociênciasPOTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) 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dc.title.por.fl_str_mv |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
title |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
spellingShingle |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) Ribeiro, Mariana Fernandes Cacau, Câncer, Nanotecnologia, PML-RARA, Polifenóis. Cocoa, Cancer, Nanotechnology, PML RARA, Polyphenols Nanociências |
title_short |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
title_full |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
title_fullStr |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
title_full_unstemmed |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
title_sort |
POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4) |
author |
Ribeiro, Mariana Fernandes |
author_facet |
Ribeiro, Mariana Fernandes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gomes, Patrícia |
dc.contributor.advisor-co1.fl_str_mv |
Cadoná, Francine |
dc.contributor.referee1.fl_str_mv |
Bagatini, Margarete Dulce |
dc.contributor.referee2.fl_str_mv |
Silva, William Leonardo da |
dc.contributor.author.fl_str_mv |
Ribeiro, Mariana Fernandes |
contributor_str_mv |
Gomes, Patrícia Cadoná, Francine Bagatini, Margarete Dulce Silva, William Leonardo da |
dc.subject.por.fl_str_mv |
Cacau, Câncer, Nanotecnologia, PML-RARA, Polifenóis. |
topic |
Cacau, Câncer, Nanotecnologia, PML-RARA, Polifenóis. Cocoa, Cancer, Nanotechnology, PML RARA, Polyphenols Nanociências |
dc.subject.eng.fl_str_mv |
Cocoa, Cancer, Nanotechnology, PML RARA, Polyphenols |
dc.subject.cnpq.fl_str_mv |
Nanociências |
description |
Acute promyelocytic leukemia is highlighted by the fusion of the PML-RARA genes causing cellular immaturity and accelerated proliferation of promyelocytes, causing symptoms such as hemorrhagic crises. Despite the efficacy of drugs such as all-trans retinoic acid and arsenic trioxide, some patients have important adverse reactions. Studies indicate that natural products are capable of acting in a chemotherapeutic manner with no or low adverse effect. In this context, cocoa (Theobroma cacao L.) was investigated for containing a chemical matrix rich in polyphenols and methylxanthines, capable of acting in an anti-tumor, anti- inflammatory and antioxidant manner. Due to its low bioavailability, an outbreak of nanotechnology as an efficient alternative to provide and improve the solubility of compounds through liposomal nanocarriers. The present study aims to evaluate the potential antitumor effect of liposomes containing cocoa against acute promyelocytic leukemia cells. Liposomes containing cocoa powder were collected in procedures of 1, 2 and 3 mg / mL-1 by the reverse phase evaporation method. The formulations produced were stored at room temperature (RT) (24 ± 2 ºC), refrigeration (RE) (4 ± 2 ºC) and climatic chamber (CC) (40 ºC 75% relative humidity) for evaluation during 90-day stability. Average particle diameter, polydispersity index, pH, catechin and methylxanthine content, encapsulation efficiency and organoleptic characteristics were adopted. Subsequently, a possible cytotoxic effect of liposomes and free cocoa was evaluated on fibroblast cell line (HFF-1) and acute promyelocytic leukemia (NB-4) from cell viability and levels of reactive oxygen species. Liposomes containing 1 mg / mL- 'remained stable for 30 days when stored in refrigeration, particle volume of 216.8 nm, polydispersity index of 0.375, zeta potential of -7.27 mV, pH 5.55 and content 3.23% theobromine, 0.74% theophylline, 1.11% catechin, 1.59% caffeine. In in vitro tests, the HFF-1 strain did not show reduced cell viability and proliferation in a reduced way. Still, it was found that the NB-4 cells dissipated cell proliferation and increased levels of reactive oxygen species within 72 hours in both treatments. It is concluded that liposomes are promising nanostructures for the encapsulation of catechins and methylxanthines as the compounds present in cocoa, in addition to having a potential carginogenic effect in acute promyelocytic leukemia cells. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-06-30T14:15:28Z |
dc.date.issued.fl_str_mv |
2021-03-26 |
dc.date.available.fl_str_mv |
2022-05-22 |
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 |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Ribeiro, Mariana Fernandes. POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4). 2021. 69f. Dissertação( Programa de Pós-Graduação em Nanociências) - Universidade Franciscana, Santa Maria - RS . |
dc.identifier.uri.fl_str_mv |
http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/998 |
identifier_str_mv |
Ribeiro, Mariana Fernandes. POTENCIAL EFEITO ANTITUMORAL DO CACAU (Theobroma cacao L.) EM LIPOSSOMAS FRENTE A CÉLULAS DE LEUCEMIA PROMIELOCÍTICA AGUDA (NB-4). 2021. 69f. Dissertação( Programa de Pós-Graduação em Nanociências) - Universidade Franciscana, Santa Maria - RS . |
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http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/998 |
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por |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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Universidade Franciscana |
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Programa de Pós-Graduação em Nanociências |
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UFN |
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Brasil |
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Biociências e Nanomateriais |
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Universidade Franciscana |
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