DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO

Detalhes bibliográficos
Autor(a) principal: Nishihira, Vivian Shinobu Kishimoto
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional Universidade Franciscana
Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/806
Resumo: In recent decades, dietary manipulation has been one of the strategies to solve health problems, since nutraceuticals, natural products, extracts and bioactives have been used with a therapeutic approach. Among the bioactives are curcumin, with a high antioxidant and anti-inflammatory power, and capsaicin, which favors its uptake after oral ingestion. However, both have low aqueous solubility, a feature that makes it difficult to use them in clinical trials, and oral bioavailability, indicating a small use. To circumvent these problems, incorporating them into solid lipid nanoparticle (SLN) may allow for more efficient delivery. The development and application of new nanotechnological products are increasing in the pharmaceutical and medical areas, especially pharmaceutical nanocarriers. Given this context, this thesis is original and innovative because, for the first time, an SLN containing curcumin and capsaicin (NCC) was produced for therapeutic purposes. The method of production known as high shear rate proved to be efficient, since particles with an average size of 112 ± 4 nm, PDI of 0.242 ± 0.00 with zeta potential of -5.62 ± 0.89 mV and pH of 5.83 ± 0.32, which were analyzed by dynamic light scattering. Simulation tests confirmed the affinity between these bioactives for albumin for hydrophobic bonds. Thus, surfactants have a lower affinity for albumin than free curcumin and capsaicin. Already the test of formation of the corona protein, in contact with the culture medium, showed that the NCC shape after 24 hours in the three concentrations (5, 12 and 24 μg/mL for curcumin and 0.17, 0.4 and 0,8 μg/mL for capsaicin) that were evaluated. Cytotoxicity in biological systems showed that the NCC, at 5 μg/mL, did not alter the cell viability in the vero and RAW264.7 cultures after 24 and 48 hours. In hemolytic activity, the concentration of 50 μg/mL did not cause haemolysis at any of the times (10 - 80 min) evaluated. The antioxidant activity of the NCC was equated to its free form (CC) by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, indicating that during NCC development it was preserved. NCC did not show genotoxicity in plasmid DNA in vitro and showed no difference in the weight of collected tissues such as liver, kidney and spleen in the in vivo toxicity assay. Based on the results obtained, it is concluded that the NCC seem safe to use and evaluated for future therapeutic purposes.
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spelling Rech, Virgínia CieloLaporta, Luciane VariniVaucher, Rodrigo de AlmeidaWannmacher, Clovis Milton DuvalIaniski, Francine RodriguesRhoden, Cristiano Rodrigo BohnSilva, William Leonardo daNishihira, Vivian Shinobu Kishimoto2019-09-11T13:40:28Z2019-03-27Nishihira, Vivian Shinobu Kishimoto. DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO. 2019. 177f. Tese( Programa de Pós-Graduação em Nanociências) - Universidade Franciscana, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/806In recent decades, dietary manipulation has been one of the strategies to solve health problems, since nutraceuticals, natural products, extracts and bioactives have been used with a therapeutic approach. Among the bioactives are curcumin, with a high antioxidant and anti-inflammatory power, and capsaicin, which favors its uptake after oral ingestion. However, both have low aqueous solubility, a feature that makes it difficult to use them in clinical trials, and oral bioavailability, indicating a small use. To circumvent these problems, incorporating them into solid lipid nanoparticle (SLN) may allow for more efficient delivery. The development and application of new nanotechnological products are increasing in the pharmaceutical and medical areas, especially pharmaceutical nanocarriers. Given this context, this thesis is original and innovative because, for the first time, an SLN containing curcumin and capsaicin (NCC) was produced for therapeutic purposes. The method of production known as high shear rate proved to be efficient, since particles with an average size of 112 ± 4 nm, PDI of 0.242 ± 0.00 with zeta potential of -5.62 ± 0.89 mV and pH of 5.83 ± 0.32, which were analyzed by dynamic light scattering. Simulation tests confirmed the affinity between these bioactives for albumin for hydrophobic bonds. Thus, surfactants have a lower affinity for albumin than free curcumin and capsaicin. Already the test of formation of the corona protein, in contact with the culture medium, showed that the NCC shape after 24 hours in the three concentrations (5, 12 and 24 μg/mL for curcumin and 0.17, 0.4 and 0,8 μg/mL for capsaicin) that were evaluated. Cytotoxicity in biological systems showed that the NCC, at 5 μg/mL, did not alter the cell viability in the vero and RAW264.7 cultures after 24 and 48 hours. In hemolytic activity, the concentration of 50 μg/mL did not cause haemolysis at any of the times (10 - 80 min) evaluated. The antioxidant activity of the NCC was equated to its free form (CC) by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, indicating that during NCC development it was preserved. NCC did not show genotoxicity in plasmid DNA in vitro and showed no difference in the weight of collected tissues such as liver, kidney and spleen in the in vivo toxicity assay. Based on the results obtained, it is concluded that the NCC seem safe to use and evaluated for future therapeutic purposes.Nas últimas décadas, a manipulação dietética tem sido uma das estratégias para resolver problemas de saúde, uma vez que nutracêuticos, produtos naturais, extratos e bioativos vêm sendo utilizados com abordagem terapêutica. Entre os bioativos, destacam-se a curcumina, com alto poder antioxidante e anti-inflamatório, e a capsaicina, que favorece a captação dessa, após sua ingestão oral. Entretanto, ambos apresentam baixas solubilidade aquosa, característica que dificulta utilizá-los em ensaios clínicos, e biodisponibilidade por via oral, indicando um pequeno aproveitamento. Para contornar esses problemas, incorporá-los em nanopartícula lipídica sólida (NLS) poderá permitir uma entrega mais eficiente. O desenvolvimento e a aplicação de novos produtos nanotecnológicos são crescentes nas áreas farmacêutica e médica, destacando-se os nanocarreadores farmacêuticos. Diante desse contexto, esta tese é original e inovadora porque, pela primeira vez, foi produzida uma NLS contendo curcumina e capsaicina (NCC) com finalidade terapêutica. O método de produção conhecido como alta taxa de cisalhamento demonstrou ser eficiente, pois foram obtidas partículas com tamanho médio de 112 ± 4 nm, PDI de 0,242 ± 0,00 com potencial zeta de -5,62 ± 0,89 mV e pH de 5,83 ± 0,32, que foram analisados por espalhamento de luz dinâmica Os testes de simulação confirmaram a afinidade entre esses bioativos pela albumina por ligações hidrofóbicas. Desse modo, os tensoativos apresentam uma afinidade menor pela albumina que a curcumina e a capsaicina livres. Já o teste de formação da corona proteica, em contato com o meio de cultura, mostrou que a NCC a forma após 24 horas nas três concentrações (5, 12 e 24 μg/mL para curcumina e 0,17, 0,4 e 0,8 μg/mL para capsaicina) que foram avaliadas. A citotoxicidade em sistemas biológicos mostrou que a NCC, na concentração de 5 μg/mL, não alterou a viabilidade celular em cultura da linhagem vero e RAW264,7, após 24 e 48 horas. Na atividade hemolítica, a concentração de 50 μg/mL não causou hemólise, em nenhum dos tempos (10 – 80 min) avaliados. A atividade antioxidante das NCC equiparou-se a sua forma livre (CC) pelo método de 1,1-difenil-2-picrilhidrazil (DPPH), indicando que, durante o desenvolvimento das NCC, foi preservada. As NCC não apresentaram genotoxicidade, no DNA plasmidial in vitro, e não mostraram nenhuma diferença no peso dos tecidos coletados, como fígado, rim e baço, no ensaio de toxicidade in vivo. Com base nos resultados obtidos, conclui-se que as NCC parecem seguras para serem utilizadas e avaliadas para fins terapêuticos futuros.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2019-09-11T13:40:28Z No. of bitstreams: 2 Tese_VivianShinobuKishimotoNishihira.pdf: 4383258 bytes, checksum: 4e157bd2a321c02c25b4b04da35fd03b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-09-11T13:40:28Z (GMT). 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dc.title.por.fl_str_mv DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
title DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
spellingShingle DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
Nishihira, Vivian Shinobu Kishimoto
Especiarias; Nanotecnologia; Solubilidade; Nanotoxicologia.
Spicy, nanotechnology, solubility, nanotoxicology
Nanociências
title_short DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
title_full DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
title_fullStr DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
title_full_unstemmed DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
title_sort DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO
author Nishihira, Vivian Shinobu Kishimoto
author_facet Nishihira, Vivian Shinobu Kishimoto
author_role author
dc.contributor.advisor1.fl_str_mv Rech, Virgínia Cielo
dc.contributor.advisor-co1.fl_str_mv Laporta, Luciane Varini
dc.contributor.advisor-co2.fl_str_mv Vaucher, Rodrigo de Almeida
dc.contributor.referee1.fl_str_mv Wannmacher, Clovis Milton Duval
dc.contributor.referee2.fl_str_mv Ianiski, Francine Rodrigues
dc.contributor.referee3.fl_str_mv Rhoden, Cristiano Rodrigo Bohn
dc.contributor.referee4.fl_str_mv Silva, William Leonardo da
dc.contributor.author.fl_str_mv Nishihira, Vivian Shinobu Kishimoto
contributor_str_mv Rech, Virgínia Cielo
Laporta, Luciane Varini
Vaucher, Rodrigo de Almeida
Wannmacher, Clovis Milton Duval
Ianiski, Francine Rodrigues
Rhoden, Cristiano Rodrigo Bohn
Silva, William Leonardo da
dc.subject.por.fl_str_mv Especiarias; Nanotecnologia; Solubilidade; Nanotoxicologia.
topic Especiarias; Nanotecnologia; Solubilidade; Nanotoxicologia.
Spicy, nanotechnology, solubility, nanotoxicology
Nanociências
dc.subject.eng.fl_str_mv Spicy, nanotechnology, solubility, nanotoxicology
dc.subject.cnpq.fl_str_mv Nanociências
description In recent decades, dietary manipulation has been one of the strategies to solve health problems, since nutraceuticals, natural products, extracts and bioactives have been used with a therapeutic approach. Among the bioactives are curcumin, with a high antioxidant and anti-inflammatory power, and capsaicin, which favors its uptake after oral ingestion. However, both have low aqueous solubility, a feature that makes it difficult to use them in clinical trials, and oral bioavailability, indicating a small use. To circumvent these problems, incorporating them into solid lipid nanoparticle (SLN) may allow for more efficient delivery. The development and application of new nanotechnological products are increasing in the pharmaceutical and medical areas, especially pharmaceutical nanocarriers. Given this context, this thesis is original and innovative because, for the first time, an SLN containing curcumin and capsaicin (NCC) was produced for therapeutic purposes. The method of production known as high shear rate proved to be efficient, since particles with an average size of 112 ± 4 nm, PDI of 0.242 ± 0.00 with zeta potential of -5.62 ± 0.89 mV and pH of 5.83 ± 0.32, which were analyzed by dynamic light scattering. Simulation tests confirmed the affinity between these bioactives for albumin for hydrophobic bonds. Thus, surfactants have a lower affinity for albumin than free curcumin and capsaicin. Already the test of formation of the corona protein, in contact with the culture medium, showed that the NCC shape after 24 hours in the three concentrations (5, 12 and 24 μg/mL for curcumin and 0.17, 0.4 and 0,8 μg/mL for capsaicin) that were evaluated. Cytotoxicity in biological systems showed that the NCC, at 5 μg/mL, did not alter the cell viability in the vero and RAW264.7 cultures after 24 and 48 hours. In hemolytic activity, the concentration of 50 μg/mL did not cause haemolysis at any of the times (10 - 80 min) evaluated. The antioxidant activity of the NCC was equated to its free form (CC) by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, indicating that during NCC development it was preserved. NCC did not show genotoxicity in plasmid DNA in vitro and showed no difference in the weight of collected tissues such as liver, kidney and spleen in the in vivo toxicity assay. Based on the results obtained, it is concluded that the NCC seem safe to use and evaluated for future therapeutic purposes.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-09-11T13:40:28Z
dc.date.issued.fl_str_mv 2019-03-27
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dc.identifier.citation.fl_str_mv Nishihira, Vivian Shinobu Kishimoto. DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO. 2019. 177f. Tese( 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/806
identifier_str_mv Nishihira, Vivian Shinobu Kishimoto. DESENVOLVIMENTO DE NANOPARTÍCULAS CONTENDO CURCUMINA E CAPSAICINA E AVALIAÇÃO DE SUAS POTENCIAIS ATIVIDADES BIOLÓGICAS IN VITRO E IN VIVO. 2019. 177f. Tese( Programa de Pós-Graduação em Nanociências) - Universidade Franciscana, Santa Maria - RS .
url http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/806
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dc.publisher.department.fl_str_mv Biociências e Nanomateriais
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