DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA

Detalhes bibliográficos
Autor(a) principal: Lima, Thiellen Wrobel Kultz de
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do UNICENTRO
Texto Completo: http://tede.unicentro.br:8080/jspui/handle/jspui/1716
Resumo: Chrysin is a flavonoid widely found in bee plants and bee products such as honey and propolis. This natural product has been being studied by many researchers due to the broad spectrum of biological activities, such as anti-inflammatory, antioxidant, and antitumor activities, among others. Despite this broad spectrum of action, chrysin has low water solubility, low stability in biological fluids, and low cell adhesion, which can affect its absorption by the body. Nanotechnology is a tool that helps to reduce these effects, increasing solubility and stability characteristics of molecules, promoting enhancing delivery of the molecule to a specific site of action. Thus, this work aimed to develop a nanostructured system using a lipid matrix with methyl palmitate and ethyl palmitate for chrysin carrying through the high-shear homogenization technique. According to the development of factorial design, a formulation was optimized and characterized by evaluating the encapsulation efficiency, particle diameter, polydispersion index, zeta potential, and morphology by scanning electron microscopy technique. The optimized nanoparticle had a size of 332.8 nm, with a polydispersion index of 0.27 and an encapsulation efficiency of 99.28%. In the stability study, the system remained stable in suspension for only a month and a lyophilized system did not obtain proven stability. Toxicity tests against red blood cells and inhibition of the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) radical were also evaluated. The results showed the effectiveness of the chrysin nanoparticle, with inhibition of approximately 72% to the hemolysis assay in 10 μg/mL. The nanoparticle was not toxic during the entire period of the study. The release assays in gastric (pH 1.2) and intestinal (pH 6.8) fluid and in phosphate buffer (pH 7.4) shows resulted in low percentages of release. It can be related to the metabolization of chrysin throughout the process. The pharmacokinetic assay demonstrated the efficiency of the chrysin encapsulation by the solid lipid nanoparticle formed, with improvement in the pharmacokinetic profile comparing to chrysin administered. Increasing the maximum concentration 141.56 ng/mL and 313.02 ng/mL for chrysin and chrysin nanoparticles, respectively. This work reveals the development and broad application potential of a chrysin-carrying lipid nanoparticle due to the innovation in using a lipid matrix composed of two distinct lipids and a prominent bioactive compound. The results obtained can be used as a basis for future research involving the association between methyl palmitate, ethyl palmitate, and chrysin.
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spelling Khalil, Najeh Maissarhttp://lattes.cnpq.br/8578241611510102Mainardes, Rubiana Marahttp://lattes.cnpq.br/7632867790178003079839159-69http://lattes.cnpq.br/0837502001376499Lima, Thiellen Wrobel Kultz de2021-09-28T14:02:40Z2021-07-23Lima, Thiellen Wrobel Kultz de. DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA. 2021. 123 f. Tese (Programa de Pós-Graduação em Química - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.http://tede.unicentro.br:8080/jspui/handle/jspui/1716Chrysin is a flavonoid widely found in bee plants and bee products such as honey and propolis. This natural product has been being studied by many researchers due to the broad spectrum of biological activities, such as anti-inflammatory, antioxidant, and antitumor activities, among others. Despite this broad spectrum of action, chrysin has low water solubility, low stability in biological fluids, and low cell adhesion, which can affect its absorption by the body. Nanotechnology is a tool that helps to reduce these effects, increasing solubility and stability characteristics of molecules, promoting enhancing delivery of the molecule to a specific site of action. Thus, this work aimed to develop a nanostructured system using a lipid matrix with methyl palmitate and ethyl palmitate for chrysin carrying through the high-shear homogenization technique. According to the development of factorial design, a formulation was optimized and characterized by evaluating the encapsulation efficiency, particle diameter, polydispersion index, zeta potential, and morphology by scanning electron microscopy technique. The optimized nanoparticle had a size of 332.8 nm, with a polydispersion index of 0.27 and an encapsulation efficiency of 99.28%. In the stability study, the system remained stable in suspension for only a month and a lyophilized system did not obtain proven stability. Toxicity tests against red blood cells and inhibition of the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) radical were also evaluated. The results showed the effectiveness of the chrysin nanoparticle, with inhibition of approximately 72% to the hemolysis assay in 10 μg/mL. The nanoparticle was not toxic during the entire period of the study. The release assays in gastric (pH 1.2) and intestinal (pH 6.8) fluid and in phosphate buffer (pH 7.4) shows resulted in low percentages of release. It can be related to the metabolization of chrysin throughout the process. The pharmacokinetic assay demonstrated the efficiency of the chrysin encapsulation by the solid lipid nanoparticle formed, with improvement in the pharmacokinetic profile comparing to chrysin administered. Increasing the maximum concentration 141.56 ng/mL and 313.02 ng/mL for chrysin and chrysin nanoparticles, respectively. This work reveals the development and broad application potential of a chrysin-carrying lipid nanoparticle due to the innovation in using a lipid matrix composed of two distinct lipids and a prominent bioactive compound. The results obtained can be used as a basis for future research involving the association between methyl palmitate, ethyl palmitate, and chrysin.A crisina é um flavonoide amplamente encontrado em plantas e produtos apícolas, como mel e própolis. Este produto natural vem sendo alvo de estudo de muitos pesquisadores devido ao seu amplo espectro de atividades biológicas, tais como atividade anti-inflamatória, antioxidante, antitumoral, entre outras. Apesar desse amplo espectro de ação, a crisina apresenta baixa solubilidade em água, baixa estabilidade em fluídos biológicos e baixa adesão celular, o que pode afetar sua absorção pelo organismo. A nanotecnologia é uma ferramenta que auxilia na redução desses efeitos, aumentando características de solubilidade e estabilidade de moléculas, promovendo maior entrega da molécula em um local específico de ação. Nesse sentido, este trabalho teve como objetivo o desenvolvimento de um sistema nanoestruturado utilizando uma matriz lipídica com palmitato de metila e palmitato de etila para carregamento da crisina através da técnica de homogeneização de alto cisalhamento. Por meio do desenvolvimento do planejamento fatorial uma formulação pode ser otimizada e caracterizada, via da determinação da eficiência de encapsulação, diâmetro de partícula, índice de polidispersão e o potencial zeta, bem como sua morfologia pela técnica de microscopia eletrônica de varredura. A nanopartícula otimizada apresentou tamanho de 332,8 nm, com índice de polidispersão de 0,27 e eficiência de encapsulação de 99,28 %. No estudo de estabilidade, o sistema se manteve estável em suspensão pelo período de 1 mês apenas e os sistemas liofilizados não obtiveram estabilidade comprovada. Foram realizados também, ensaios de toxicidade frente a hemácias e de inibição do radical 2,2´-azinobis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS•+). Os resultados mostraram a eficácia da nanopartícula com crisina na concentração de 10 μg/mL com uma porcentagem de inibição de aproximadamente 72 % e com relação ao ensaio de hemólise, a nanopartícula não se mostrou tóxica durante todo o período estudado. Os ensaios de liberação em fluído gástrico (pH 1,2) e intestinal (pH 6,8) e tampão fosfato (pH 7,4) resultaram em porcentagens baixas de liberação, podendo ser justificados pela metabolização da crisina ao longo do processo. A validação do método UPLC-MS na determinação de crisina em plasma de ratos foi realizada de acordo com os parâmetros estabelecidos. O ensaio de farmacocinética demonstrou a eficiência do processo de encapsulação de crisina pela nanopartícula sólida lipídica formada, com melhora no perfil farmacocinético em comparação com a crisina administrada de maneira livre. Isso, considerando o aumentando a concentração máxima de 141,56 ng/mL para 313,02 ng/mL, para crisina e nanopartícula de crisina, respectivamente. Este trabalho revela o desenvolvimento e amplo potencial de aplicações de uma nanopartícula lipídica carregadora de crisina, devido à inovação em usar uma matriz lipídica composta por dois lipídeos distintos e um composto bioativo de destaque. Os resultados obtidos podem ser utilizados como base para pesquisas futuras envolvendo a associação entre palmitato de metila, palmitato de etila e crisina.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2021-09-28T14:02:40Z No. of bitstreams: 1 Tese THIELLEN WROBEL KULTZ DE LIMA.pdf: 2272927 bytes, checksum: c6148189b9155512684ba9cad766b3d4 (MD5)Made available in DSpace on 2021-09-28T14:02:40Z (GMT). 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dc.title.por.fl_str_mv DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
title DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
spellingShingle DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
Lima, Thiellen Wrobel Kultz de
nanopartículas sólidas lipídicas
crisina
farmacocinética
solid lipid nanoparticles
chrysin
pharmacokinetics
CIENCIAS EXATAS E DA TERRA::QUIMICA
title_short DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
title_full DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
title_fullStr DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
title_full_unstemmed DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
title_sort DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA
author Lima, Thiellen Wrobel Kultz de
author_facet Lima, Thiellen Wrobel Kultz de
author_role author
dc.contributor.advisor1.fl_str_mv Khalil, Najeh Maissar
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8578241611510102
dc.contributor.advisor-co1.fl_str_mv Mainardes, Rubiana Mara
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/7632867790178003
dc.contributor.authorID.fl_str_mv 079839159-69
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0837502001376499
dc.contributor.author.fl_str_mv Lima, Thiellen Wrobel Kultz de
contributor_str_mv Khalil, Najeh Maissar
Mainardes, Rubiana Mara
dc.subject.por.fl_str_mv nanopartículas sólidas lipídicas
crisina
farmacocinética
topic nanopartículas sólidas lipídicas
crisina
farmacocinética
solid lipid nanoparticles
chrysin
pharmacokinetics
CIENCIAS EXATAS E DA TERRA::QUIMICA
dc.subject.eng.fl_str_mv solid lipid nanoparticles
chrysin
pharmacokinetics
dc.subject.cnpq.fl_str_mv CIENCIAS EXATAS E DA TERRA::QUIMICA
description Chrysin is a flavonoid widely found in bee plants and bee products such as honey and propolis. This natural product has been being studied by many researchers due to the broad spectrum of biological activities, such as anti-inflammatory, antioxidant, and antitumor activities, among others. Despite this broad spectrum of action, chrysin has low water solubility, low stability in biological fluids, and low cell adhesion, which can affect its absorption by the body. Nanotechnology is a tool that helps to reduce these effects, increasing solubility and stability characteristics of molecules, promoting enhancing delivery of the molecule to a specific site of action. Thus, this work aimed to develop a nanostructured system using a lipid matrix with methyl palmitate and ethyl palmitate for chrysin carrying through the high-shear homogenization technique. According to the development of factorial design, a formulation was optimized and characterized by evaluating the encapsulation efficiency, particle diameter, polydispersion index, zeta potential, and morphology by scanning electron microscopy technique. The optimized nanoparticle had a size of 332.8 nm, with a polydispersion index of 0.27 and an encapsulation efficiency of 99.28%. In the stability study, the system remained stable in suspension for only a month and a lyophilized system did not obtain proven stability. Toxicity tests against red blood cells and inhibition of the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) radical were also evaluated. The results showed the effectiveness of the chrysin nanoparticle, with inhibition of approximately 72% to the hemolysis assay in 10 μg/mL. The nanoparticle was not toxic during the entire period of the study. The release assays in gastric (pH 1.2) and intestinal (pH 6.8) fluid and in phosphate buffer (pH 7.4) shows resulted in low percentages of release. It can be related to the metabolization of chrysin throughout the process. The pharmacokinetic assay demonstrated the efficiency of the chrysin encapsulation by the solid lipid nanoparticle formed, with improvement in the pharmacokinetic profile comparing to chrysin administered. Increasing the maximum concentration 141.56 ng/mL and 313.02 ng/mL for chrysin and chrysin nanoparticles, respectively. This work reveals the development and broad application potential of a chrysin-carrying lipid nanoparticle due to the innovation in using a lipid matrix composed of two distinct lipids and a prominent bioactive compound. The results obtained can be used as a basis for future research involving the association between methyl palmitate, ethyl palmitate, and chrysin.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-09-28T14:02:40Z
dc.date.issued.fl_str_mv 2021-07-23
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv Lima, Thiellen Wrobel Kultz de. DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA. 2021. 123 f. Tese (Programa de Pós-Graduação em Química - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.
dc.identifier.uri.fl_str_mv http://tede.unicentro.br:8080/jspui/handle/jspui/1716
identifier_str_mv Lima, Thiellen Wrobel Kultz de. DESENVOLVIMENTO, CARACTERIZAÇÃO E AVALIAÇÃO BIOLÓGICA DE NANOPARTÍCULAS LIPÍDICAS CONTENDO CRISINA. 2021. 123 f. Tese (Programa de Pós-Graduação em Química - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.
url http://tede.unicentro.br:8080/jspui/handle/jspui/1716
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 3800526532796635565
dc.relation.confidence.fl_str_mv 600
600
600
600
dc.relation.department.fl_str_mv -4338065490277529033
dc.relation.cnpq.fl_str_mv 1571700325303117195
dc.relation.sponsorship.fl_str_mv 2075167498588264571
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Estadual do Centro-Oeste
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Química (Doutorado)
dc.publisher.initials.fl_str_mv UNICENTRO
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Unicentro::Departamento de Ciências Exatas e de Tecnologia
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