Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model

Detalhes bibliográficos
Autor(a) principal: Franco, Camila
Data de Publicação: 2022
Outros Autores: Viana, Altevir Rossato, Ourique, Aline Ferreira, Vizzotto, Bruno Stefanello, Krause, Luciana Maria Fontanari
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Revista Brasileira de Cancerologia (Online)
Texto Completo: https://rbc.inca.gov.br/index.php/revista/article/view/2545
Resumo: Introduction: Anti-inflammatory drugs are being utilized to treat cancer because of its inflammatory microenvironment. Objective: The objective of this study is to investigate the antioxidant potential of indomethacin and its genotoxicity, since free or loaded in polymeric nanocapsules using MCF-7 (human breast cancer) cells as an in vitro model. Method: Development of indomethacin-loaded polyepsiloncaprolactone (PCL) nanocapsules by interfacial deposition method. It is characterized by pH determination by potentiometer, mean diameter and polydispersity index by dynamic light scattering; zeta potential by electrophoretic mobility; encapsulation efficacy by high performance liquid chromatography method; corona effect formation; 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) method by spectrofluorimetric assay; nitric oxide (NO) determination by spectrophotometric and genotoxicity assay by plasmid DNA cleavage method. Results: The results showed a mild acidic pH (4.78 ± 0.10), sizes around 200 nm and PDI<0.2 with a zeta potential around -20 mV and encapsulation efficiency of 99% (1 mg mL-1), showing a dose-dependent corona formation profile in 24h incubation. Conclusion: DCFH-DA assay showed no production of reactive oxygen species (ROS) while NO determination showed that Ind-OH-NC from 26.7 to 100 μM increased reactive nitrogen species (RNS), demonstrating antioxidant potential against MCF-7 cells. No sample at the concentrations evaluated induced DNA cleavage, being considered a safe treatment.
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spelling Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell ModelEfecto Protector de Nanopartículas Poliméricas con Indometacina contra la Citotoxicidad Inducida por Estrés Oxidativo en Modelo de Células de Adenocarcinoma de Mama HumanoEfeito Protetor de Nanopartículas Poliméricas com Indometacina contra Citotoxicidade Induzida por Estresse Oxidativo em Modelo Celular de Adenocarcinoma de Mama Humanoindomethacin/pharmacologyantioxidantsnanocapsulesneoplasmsindometacina/farmacologíaantioxidantesnanocápsulasneoplasiasindometacina/farmacologiaantioxidantesnanocápsulasneoplasiasIntroduction: Anti-inflammatory drugs are being utilized to treat cancer because of its inflammatory microenvironment. Objective: The objective of this study is to investigate the antioxidant potential of indomethacin and its genotoxicity, since free or loaded in polymeric nanocapsules using MCF-7 (human breast cancer) cells as an in vitro model. Method: Development of indomethacin-loaded polyepsiloncaprolactone (PCL) nanocapsules by interfacial deposition method. It is characterized by pH determination by potentiometer, mean diameter and polydispersity index by dynamic light scattering; zeta potential by electrophoretic mobility; encapsulation efficacy by high performance liquid chromatography method; corona effect formation; 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) method by spectrofluorimetric assay; nitric oxide (NO) determination by spectrophotometric and genotoxicity assay by plasmid DNA cleavage method. Results: The results showed a mild acidic pH (4.78 ± 0.10), sizes around 200 nm and PDI<0.2 with a zeta potential around -20 mV and encapsulation efficiency of 99% (1 mg mL-1), showing a dose-dependent corona formation profile in 24h incubation. Conclusion: DCFH-DA assay showed no production of reactive oxygen species (ROS) while NO determination showed that Ind-OH-NC from 26.7 to 100 μM increased reactive nitrogen species (RNS), demonstrating antioxidant potential against MCF-7 cells. No sample at the concentrations evaluated induced DNA cleavage, being considered a safe treatment.Introducción: Se están utilizando antiinflamatorios para tratamiento de cáncer debido a su entorno inflamado. Objetivo: Investigar el potencial antioxidante de la indometacina y su genotoxicidad, libre o acarreada en nanocápsulas poliméricas utilizando como modelo in vitro células MCF-7 (cáncer de mama humano). Método: Desarrollo de nanocápsulas de poli epsilon-caprolactona (PCL) por método de deposición interfacial, caracterizada por determinación de pH por potenciómetro; diámetro medio e índice de polidispersión por esparcimiento dinámico de luz; potencial zeta por movilidad electroforética; eficiencia de encapsulación por cromatografía líquida de alta eficiencia; formación de efecto corona; método de 2’,7’-diclorofluoresceína diacetato (DCFH-DA) por ensayo espectrofluorímetro; determinación de óxido nítrico (NO) por espectrometría y ensayo de genotoxicidad por método de clivaje del ADN plasmídico. Resultados: Los resultados mostraron ligero pH ácido (4,78 ± 0,10), tamaños alrededor de 200 nm y PDI<0,2 con potencial zeta alrededor de -20 mV y eficiencia de encapsulación de 99% (1 mg mL-1), presentando perfil de formación de corona dosis-dependiente en 24h de incubación. Conclusión: El ensayo DCFDA mostró que no hay producción de especies reactivas de oxígeno (ROS) mientras que la determinación de NO mostró que Ind-OH-NC de 26,7 a 100 μM aumentó las especies reactivas de nitrógeno (RNS), demostrando potencial antioxidante contra MCF-7. Ninguna muestra en las concentraciones evaluadas indujo clivaje del ADN, siendo considerado un tratamiento seguro.Introdução: Anti-inflamatórios estão sendo empregados para tratamento de câncer por causa do seu ambiente inflamado. Objetivo: Investigar o potencial antioxidante da indometacina e sua genotoxicidade, livre ou carreada em nanocápsulas poliméricas, usando como modelo in vitro células MCF-7 (câncer de mama humano). Método: Desenvolvimento de nanocápsulas de poliepsilon-caprolactona (PCL) por método de deposição interfacial, caracterizada por determinação de pH por potenciômetro; diâmetro médio e índice de polidispersão por espalhamento dinâmico de luz; potencial zeta por mobilidade eletroforética; eficiência de encapsulação por cromatografia líquida de alta eficiência; formação de efeito corona; método de 2’,7’-diclorofluoresceína diacetato (DCFH-DA) por ensaio espectrofluorimétrico; determinação de óxido nítrico (NO) por espectrometria e ensaio de genotoxicidade por método de clivagem do DNA plasmidial. Resultados: Os resultados mostraram leve pH ácido (4,78 ± 0,10), tamanhos em torno de 200 nm e PDI<0,2 com potencial zeta em torno de -20 mV e eficiência de encapsulação de 99% (1 mg mL-1), apresentando perfil de formação de corona dose-dependente em 24 horas de incubação. Conclusão: O ensaio DCFH-DA mostrou que não há produção de espécies reativas de oxigênio (ROS), enquanto a determinação de NO mostrou que Ind-OH-NC de 26,7 a 100 μM aumentou as espécies reativas de nitrogênio (RNS), demonstrando potencial antioxidante contra MCF-7. Nenhuma amostra nas concentrações avaliadas induziu clivagem do DNA, sendo considerado um tratamento seguro.INCA2022-09-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArtigos, Avaliado pelos paresapplication/pdftext/htmlhttps://rbc.inca.gov.br/index.php/revista/article/view/254510.32635/2176-9745.RBC.2022v68n4.2545Revista Brasileira de Cancerologia; Vol. 68 No. 4 (2022): Oct./Nov./Dec.; e-012545Revista Brasileira de Cancerologia; Vol. 68 Núm. 4 (2022): oct./nov./dic.; e-012545Revista Brasileira de Cancerologia; v. 68 n. 4 (2022): out./nov./dez.; e-0125452176-9745reponame:Revista Brasileira de Cancerologia (Online)instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)instacron:INCAenghttps://rbc.inca.gov.br/index.php/revista/article/view/2545/2154https://rbc.inca.gov.br/index.php/revista/article/view/2545/2440Copyright (c) 2022 Revista Brasileira de Cancerologiahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessFranco, CamilaViana, Altevir RossatoOurique, Aline FerreiraVizzotto, Bruno StefanelloKrause, Luciana Maria Fontanari2022-12-13T15:06:32Zoai:rbc.inca.gov.br:article/2545Revistahttps://rbc.inca.gov.br/index.php/revistaPUBhttps://rbc.inca.gov.br/index.php/revista/oairbc@inca.gov.br0034-71162176-9745opendoar:2022-12-13T15:06:32Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)false
dc.title.none.fl_str_mv Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
Efecto Protector de Nanopartículas Poliméricas con Indometacina contra la Citotoxicidad Inducida por Estrés Oxidativo en Modelo de Células de Adenocarcinoma de Mama Humano
Efeito Protetor de Nanopartículas Poliméricas com Indometacina contra Citotoxicidade Induzida por Estresse Oxidativo em Modelo Celular de Adenocarcinoma de Mama Humano
title Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
spellingShingle Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
Franco, Camila
indomethacin/pharmacology
antioxidants
nanocapsules
neoplasms
indometacina/farmacología
antioxidantes
nanocápsulas
neoplasias
indometacina/farmacologia
antioxidantes
nanocápsulas
neoplasias
title_short Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
title_full Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
title_fullStr Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
title_full_unstemmed Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
title_sort Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
author Franco, Camila
author_facet Franco, Camila
Viana, Altevir Rossato
Ourique, Aline Ferreira
Vizzotto, Bruno Stefanello
Krause, Luciana Maria Fontanari
author_role author
author2 Viana, Altevir Rossato
Ourique, Aline Ferreira
Vizzotto, Bruno Stefanello
Krause, Luciana Maria Fontanari
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Franco, Camila
Viana, Altevir Rossato
Ourique, Aline Ferreira
Vizzotto, Bruno Stefanello
Krause, Luciana Maria Fontanari
dc.subject.por.fl_str_mv indomethacin/pharmacology
antioxidants
nanocapsules
neoplasms
indometacina/farmacología
antioxidantes
nanocápsulas
neoplasias
indometacina/farmacologia
antioxidantes
nanocápsulas
neoplasias
topic indomethacin/pharmacology
antioxidants
nanocapsules
neoplasms
indometacina/farmacología
antioxidantes
nanocápsulas
neoplasias
indometacina/farmacologia
antioxidantes
nanocápsulas
neoplasias
description Introduction: Anti-inflammatory drugs are being utilized to treat cancer because of its inflammatory microenvironment. Objective: The objective of this study is to investigate the antioxidant potential of indomethacin and its genotoxicity, since free or loaded in polymeric nanocapsules using MCF-7 (human breast cancer) cells as an in vitro model. Method: Development of indomethacin-loaded polyepsiloncaprolactone (PCL) nanocapsules by interfacial deposition method. It is characterized by pH determination by potentiometer, mean diameter and polydispersity index by dynamic light scattering; zeta potential by electrophoretic mobility; encapsulation efficacy by high performance liquid chromatography method; corona effect formation; 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) method by spectrofluorimetric assay; nitric oxide (NO) determination by spectrophotometric and genotoxicity assay by plasmid DNA cleavage method. Results: The results showed a mild acidic pH (4.78 ± 0.10), sizes around 200 nm and PDI<0.2 with a zeta potential around -20 mV and encapsulation efficiency of 99% (1 mg mL-1), showing a dose-dependent corona formation profile in 24h incubation. Conclusion: DCFH-DA assay showed no production of reactive oxygen species (ROS) while NO determination showed that Ind-OH-NC from 26.7 to 100 μM increased reactive nitrogen species (RNS), demonstrating antioxidant potential against MCF-7 cells. No sample at the concentrations evaluated induced DNA cleavage, being considered a safe treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022-09-13
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Artigos, Avaliado pelos pares
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://rbc.inca.gov.br/index.php/revista/article/view/2545
10.32635/2176-9745.RBC.2022v68n4.2545
url https://rbc.inca.gov.br/index.php/revista/article/view/2545
identifier_str_mv 10.32635/2176-9745.RBC.2022v68n4.2545
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://rbc.inca.gov.br/index.php/revista/article/view/2545/2154
https://rbc.inca.gov.br/index.php/revista/article/view/2545/2440
dc.rights.driver.fl_str_mv Copyright (c) 2022 Revista Brasileira de Cancerologia
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Revista Brasileira de Cancerologia
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
text/html
dc.publisher.none.fl_str_mv INCA
publisher.none.fl_str_mv INCA
dc.source.none.fl_str_mv Revista Brasileira de Cancerologia; Vol. 68 No. 4 (2022): Oct./Nov./Dec.; e-012545
Revista Brasileira de Cancerologia; Vol. 68 Núm. 4 (2022): oct./nov./dic.; e-012545
Revista Brasileira de Cancerologia; v. 68 n. 4 (2022): out./nov./dez.; e-012545
2176-9745
reponame:Revista Brasileira de Cancerologia (Online)
instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
instacron:INCA
instname_str Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
instacron_str INCA
institution INCA
reponame_str Revista Brasileira de Cancerologia (Online)
collection Revista Brasileira de Cancerologia (Online)
repository.name.fl_str_mv Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
repository.mail.fl_str_mv rbc@inca.gov.br
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