DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA
Autor(a) principal: | |
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Data de Publicação: | 2017 |
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/1004 |
Resumo: | The diphenyl diselenide, (PhSe)2, is a simple selenium organocompound known for its pharmacological and toxicological effects, however, its clinical application is limited by its low aqueous solubility, which results in low bioavailability, restricting its efficacy. To overcome these limitations, this study developed polymeric nanoparticles (Nps) containing (PhSe)2 by the method of emulsification-solvent evaporation.The high-performance liquid chromatography (HPLC) coupled to a photodiode detector (PDA) was analytical method used for quantification of (PhSe)2 present in the nanoparticles. The method was validated according to current norms, mobile phase consisted of methanol and acidified water (90:10, v/v), flow 1 mL/min with detection at 240 nm. Nanoparticles of poly (lactic acid) (PLA) containing (PhSe)2 were successfully obtained, showed spherical shape and an encapsulation efficiency and mean size close to 90%, and 220 nm, respectively. The zeta potential of the formulation was -23 mV, a value that theoretically ensures physicochemical stability of the particles. The infrared analysis, X-ray diffraction, differential scanning calorimetry and thermogravimetric showed that the nanoencapsulation process promoted drug amorphation and interaction of (PhSe)2 with the polymeric matrix. The stability study shows that Nps in suspension did not show stability in the 7 days test, whereas the lyophilized Nps were stable over the 3month study both at room temperature, the chilled and frozen. The in vitro release study showed that the end of the 192 h about 61% of (PhSe)2encapsulated was released and that this release occurred by two constants, a fast and other slowly, suggesting a second order kinetics. Through the antioxidant assay was possible to observe that the process of nanoencapsulation did not alter the antioxidant potential of (PhSe)2, since after 48 hours the nanoparticles showed inhibitory capacity similar to (PhSe)2 free.In the erythrocyte cytotoxicity assay, Nps-(PhSe)2 showed lower toxicity on erythrocyte than free (PhSe)2. Finally the NPs were tested against the tumor lines (B16-F10 and HEp-2), and the results obtained were promising, since the nanoparticles of (PhSe)2 maintained the antitumor property of the compound. Thus, the PLA nanoparticles demonstrated to be potential carriers for (PhSe)2, with adequate physicochemical characteristics, lower cytotoxicity on normal cells and maintenance of antioxidant and antitumor activity. |
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Khalil, Najeh Maissarhttp://lattes.cnpq.br/8578241611510102Mainardes, Rubiana Marahttp://lattes.cnpq.br/7632867790178003056679059-90http://lattes.cnpq.br/3760071274629743ANTUNES JUNIOR, OSMAR DOS REIS2019-04-23T13:38:34Z2017-12-01ANTUNES JUNIOR, OSMAR DOS REIS. DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA. 2017. 124 f. Tese (Programa de Pós-Graduação em Química - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava - PR.http://tede.unicentro.br:8080/jspui/handle/jspui/1004The diphenyl diselenide, (PhSe)2, is a simple selenium organocompound known for its pharmacological and toxicological effects, however, its clinical application is limited by its low aqueous solubility, which results in low bioavailability, restricting its efficacy. To overcome these limitations, this study developed polymeric nanoparticles (Nps) containing (PhSe)2 by the method of emulsification-solvent evaporation.The high-performance liquid chromatography (HPLC) coupled to a photodiode detector (PDA) was analytical method used for quantification of (PhSe)2 present in the nanoparticles. The method was validated according to current norms, mobile phase consisted of methanol and acidified water (90:10, v/v), flow 1 mL/min with detection at 240 nm. Nanoparticles of poly (lactic acid) (PLA) containing (PhSe)2 were successfully obtained, showed spherical shape and an encapsulation efficiency and mean size close to 90%, and 220 nm, respectively. The zeta potential of the formulation was -23 mV, a value that theoretically ensures physicochemical stability of the particles. The infrared analysis, X-ray diffraction, differential scanning calorimetry and thermogravimetric showed that the nanoencapsulation process promoted drug amorphation and interaction of (PhSe)2 with the polymeric matrix. The stability study shows that Nps in suspension did not show stability in the 7 days test, whereas the lyophilized Nps were stable over the 3month study both at room temperature, the chilled and frozen. The in vitro release study showed that the end of the 192 h about 61% of (PhSe)2encapsulated was released and that this release occurred by two constants, a fast and other slowly, suggesting a second order kinetics. Through the antioxidant assay was possible to observe that the process of nanoencapsulation did not alter the antioxidant potential of (PhSe)2, since after 48 hours the nanoparticles showed inhibitory capacity similar to (PhSe)2 free.In the erythrocyte cytotoxicity assay, Nps-(PhSe)2 showed lower toxicity on erythrocyte than free (PhSe)2. Finally the NPs were tested against the tumor lines (B16-F10 and HEp-2), and the results obtained were promising, since the nanoparticles of (PhSe)2 maintained the antitumor property of the compound. Thus, the PLA nanoparticles demonstrated to be potential carriers for (PhSe)2, with adequate physicochemical characteristics, lower cytotoxicity on normal cells and maintenance of antioxidant and antitumor activity.O disseleneto de difenila, (PhSe)2, é um organocomposto de selênio simples, conhecido pelos seus efeitos farmacológicos e toxicológicos, porém, sua aplicação clínica é limitada devido a sua baixa solubilidade aquosa, que resulta em baixa biodisponibilidade, restringindo sua eficácia. Para superar essas limitações, o presente trabalho desenvolveu nanopartículas poliméricas (Nps) contendo (PhSe)2 através do método de emulsificação-evaporação do solvente. A cromatografia líquida de alta eficiência (CLAE) acoplada a um detector de arranjo de diodo (DAD) foi o método analítico utilizado para quantificação do (PhSe)2 presente nas nanopartículas. A validação do método foi realizada de acordo com as normatizações vigentes, a fase móvel consistiu em metanol e água acidificada (90:10, v/v), fluxo de 1 mL/min, com detecção em 240 nm. As nanopartículas de poli(ácido láctico) (PLA) contendo (PhSe)2 foram obtidas com êxito, apresentaram formato esférico e uma eficiência de encapsulação e tamanho médio próximo a 90% e 220 nm, respectivamente. O potencial zeta da formulação foi de -23 mV, valor que teoricamente garante estabilidade físico-química das partículas. As análises de infravermelho, difração de Raios X, calorimetria exploratória diferencial e termogravimetria demonstraram que o processo de nanoencapsulação promoveu amorfização do fármaco e interação do (PhSe)2 com a matriz polimérica. O estudo de estabilidade mostrou que as Nps em suspensão não apresentaram estabilidade nos 7 dias de ensaio, enquanto que as Nps liofilizadas foram estáveis durante os 3 meses de estudo tanto em temperatura ambiente, quanto refrigeradas e congeladas. O estudo de liberação in vitro mostrou que ao final das 192 h cerca de 61% do (PhSe)2 encapsulado foi liberado, e que essa liberação aconteceu através de 2 constantes, uma rápida e outra lenta, sugerindo uma cinética de segunda ordem. Através do ensaio antioxidante foi possível observar que o processo de nanoencapsulação não alterou o potencial antioxidante do (PhSe)2, uma vez que após 48 h de ensaio as nanopartículas apresentaram capacidade inibitória semelhante ao (PhSe)2 livre. No ensaio de citotoxicidade frente as hemácias, as Nps-(PhSe)2 demonstraram menor toxicidade sobre os eritrócitos que o (PhSe)2 livre. Por fim as Nps foram testadas frente as linhagens tumorais (B16-F10 e HEp-2), e os resultados obtidos foram promissores, visto que as nanopartículas de (PhSe)2 mantiveram a propriedade antitumoral do composto.Sendo assim, as nanopartículas de PLA demonstraram ser carreadores potenciais para o (PhSe)2, com características físico-químicas adequadas, menor citotoxicidade sobre células normais e manutenção da atividade antioxidante e antitumoral.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2019-04-23T13:38:34Z No. of bitstreams: 1 OSMAR DOS REIS ANTUNES JUNIOR.pdf: 2286757 bytes, checksum: a40fed5b32a08b991e6fde19eb3d1f72 (MD5)Made available in DSpace on 2019-04-23T13:38:34Z (GMT). No. of bitstreams: 1 OSMAR DOS REIS ANTUNES JUNIOR.pdf: 2286757 bytes, checksum: a40fed5b32a08b991e6fde19eb3d1f72 (MD5) Previous issue date: 2017-12-01Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede.unicentro.br:8080/jspui/retrieve/4466/OSMAR%20DOS%20REIS%20ANTUNES%20JUNIOR.pdf.jpgporUniversidade Estadual do Centro-OestePrograma de Pós-Graduação em Química (Doutorado)UNICENTROBrasilUnicentro::Departamento de Ciências Exatas e de Tecnologiadisseleneto de difenilatoxicidadeantitumoralantioxidantenanopartículas poliméricasdiphenyl diselenidetoxicityantitumorantioxidantpolymeric nanoparticlesCIENCIAS EXATAS E DA TERRA::QUIMICADESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILADevelopment and Evaluation of a Nanostructured System containing Diphenyl Diselenideinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis3800526532796635565600600600600-433806549027752903315717003253031171952075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UNICENTROinstname:Universidade Estadual do Centro-Oeste (UNICENTRO)instacron:UNICENTROTHUMBNAILOSMAR DOS REIS ANTUNES JUNIOR.pdf.jpgOSMAR DOS REIS ANTUNES JUNIOR.pdf.jpgimage/jpeg2337http://localhost:8080/tede/bitstream/jspui/1004/4/OSMAR+DOS+REIS+ANTUNES+JUNIOR.pdf.jpg70016f6d04f9f04d9dbe622d57fb7c43MD54TEXTOSMAR DOS REIS ANTUNES JUNIOR.pdf.txtOSMAR DOS REIS ANTUNES JUNIOR.pdf.txttext/plain230785http://localhost:8080/tede/bitstream/jspui/1004/3/OSMAR+DOS+REIS+ANTUNES+JUNIOR.pdf.txt5e5cf8d620a7b914626ef9675e874d35MD53ORIGINALOSMAR DOS REIS ANTUNES JUNIOR.pdfOSMAR DOS REIS ANTUNES JUNIOR.pdfapplication/pdf2286757http://localhost:8080/tede/bitstream/jspui/1004/2/OSMAR+DOS+REIS+ANTUNES+JUNIOR.pdfa40fed5b32a08b991e6fde19eb3d1f72MD52LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
dc.title.alternative.eng.fl_str_mv |
Development and Evaluation of a Nanostructured System containing Diphenyl Diselenide |
title |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
spellingShingle |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA ANTUNES JUNIOR, OSMAR DOS REIS disseleneto de difenila toxicidade antitumoral antioxidante nanopartículas poliméricas diphenyl diselenide toxicity antitumor antioxidant polymeric nanoparticles CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
title_full |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
title_fullStr |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
title_full_unstemmed |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
title_sort |
DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA |
author |
ANTUNES JUNIOR, OSMAR DOS REIS |
author_facet |
ANTUNES JUNIOR, OSMAR DOS REIS |
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 |
056679059-90 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3760071274629743 |
dc.contributor.author.fl_str_mv |
ANTUNES JUNIOR, OSMAR DOS REIS |
contributor_str_mv |
Khalil, Najeh Maissar Mainardes, Rubiana Mara |
dc.subject.por.fl_str_mv |
disseleneto de difenila toxicidade antitumoral antioxidante nanopartículas poliméricas |
topic |
disseleneto de difenila toxicidade antitumoral antioxidante nanopartículas poliméricas diphenyl diselenide toxicity antitumor antioxidant polymeric nanoparticles CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
diphenyl diselenide toxicity antitumor antioxidant polymeric nanoparticles |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
The diphenyl diselenide, (PhSe)2, is a simple selenium organocompound known for its pharmacological and toxicological effects, however, its clinical application is limited by its low aqueous solubility, which results in low bioavailability, restricting its efficacy. To overcome these limitations, this study developed polymeric nanoparticles (Nps) containing (PhSe)2 by the method of emulsification-solvent evaporation.The high-performance liquid chromatography (HPLC) coupled to a photodiode detector (PDA) was analytical method used for quantification of (PhSe)2 present in the nanoparticles. The method was validated according to current norms, mobile phase consisted of methanol and acidified water (90:10, v/v), flow 1 mL/min with detection at 240 nm. Nanoparticles of poly (lactic acid) (PLA) containing (PhSe)2 were successfully obtained, showed spherical shape and an encapsulation efficiency and mean size close to 90%, and 220 nm, respectively. The zeta potential of the formulation was -23 mV, a value that theoretically ensures physicochemical stability of the particles. The infrared analysis, X-ray diffraction, differential scanning calorimetry and thermogravimetric showed that the nanoencapsulation process promoted drug amorphation and interaction of (PhSe)2 with the polymeric matrix. The stability study shows that Nps in suspension did not show stability in the 7 days test, whereas the lyophilized Nps were stable over the 3month study both at room temperature, the chilled and frozen. The in vitro release study showed that the end of the 192 h about 61% of (PhSe)2encapsulated was released and that this release occurred by two constants, a fast and other slowly, suggesting a second order kinetics. Through the antioxidant assay was possible to observe that the process of nanoencapsulation did not alter the antioxidant potential of (PhSe)2, since after 48 hours the nanoparticles showed inhibitory capacity similar to (PhSe)2 free.In the erythrocyte cytotoxicity assay, Nps-(PhSe)2 showed lower toxicity on erythrocyte than free (PhSe)2. Finally the NPs were tested against the tumor lines (B16-F10 and HEp-2), and the results obtained were promising, since the nanoparticles of (PhSe)2 maintained the antitumor property of the compound. Thus, the PLA nanoparticles demonstrated to be potential carriers for (PhSe)2, with adequate physicochemical characteristics, lower cytotoxicity on normal cells and maintenance of antioxidant and antitumor activity. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-12-01 |
dc.date.accessioned.fl_str_mv |
2019-04-23T13:38:34Z |
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 |
ANTUNES JUNIOR, OSMAR DOS REIS. DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA. 2017. 124 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/1004 |
identifier_str_mv |
ANTUNES JUNIOR, OSMAR DOS REIS. DESENVOLVIMENTO E AVALIAÇÃO DE UM SISTEMA NANOESTRUTURADO CONTENDO DISSELENETO DE DIFENILA. 2017. 124 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/1004 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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3800526532796635565 |
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600 600 600 600 |
dc.relation.department.fl_str_mv |
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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 |
publisher.none.fl_str_mv |
Universidade Estadual do Centro-Oeste |
dc.source.none.fl_str_mv |
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Biblioteca Digital de Teses e Dissertações do UNICENTRO |
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Biblioteca Digital de Teses e Dissertações do UNICENTRO - Universidade Estadual do Centro-Oeste (UNICENTRO) |
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repositorio@unicentro.br||fabianoqueiroz@yahoo.com.br |
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1801859373447774208 |