Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , |
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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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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1797042250198286336 |