OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UNICENTRO |
Texto Completo: | http://tede.unicentro.br:8080/jspui/handle/jspui/660 |
Resumo: | Tamoxifen (TAM) is a drug widely used as an adjuvant in breast cancer therapy. Despite showing high bioavailability, has high toxicity, which may be responsible for the lack of patient adherence to treatment. The present work aimed at the development of polymeric nanoparticles as controlled release form of TAM in order to reduce possible toxicity front to healthy human cells system. The nanoparticles of poly (lactic acid) (PLA) containing citrate of tamoxifen (CTAM) were developed by the method of emulsification-solvent evaporation. An optimization procedure was performed by varying the type of surfactant (polyvinyl alcohol, polysorbate 80 or poloxamer 188) and the same concentrations (1 or 2%). The choice of the best formulation was based on features of lower mean diameter and higher encapsulation efficiency (EE%). The optimized formulation was used that 1% PVA, which had the following characteristics: 155.3 ± 4.11 nm and 85.18 ± 8.11% encapsulation of CTAM. The analysis of the drugpolymer interaction have shown that the process of nanoencapsulation generated amorphization CTAM conveyed to the nanoparticles. The in vitro release study demonstrated that CTAM has biphasic and controlled release from the nanoparticles with kinetic type of the second order coefficient Korsmeyer-Peppas indicated that the release mechanism is the diffusion-type CTAM. In the cell toxicity tests erythrocytes, nanoparticles containing CTAM showed no hemolytic potential, in contrast to free drug which showed high erythrocyte lysis. When evaluated the cytotoxicity on Hela tumor cell line, CTAM nanoencapsulado had lower cytotoxic than free CTAM, but maintained antitumor drug action. The results show that the nanoparticles have a potential for application as controlled release of antitumor treatments CTAM system. |
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Mainardes, Rubiana Marahttp://lattes.cnpq.br/7632867790178003Khalil, Najeh Maissarhttp://lattes.cnpq.br/8578241611510102005.645.369-89http://lattes.cnpq.br/2996620184791260ALTMEYER, CLESCILA2017-06-01T19:31:22Z2014-08-08ALTMEYER, CLESCILA. OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS. 2014. 90 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR.http://tede.unicentro.br:8080/jspui/handle/jspui/660Tamoxifen (TAM) is a drug widely used as an adjuvant in breast cancer therapy. Despite showing high bioavailability, has high toxicity, which may be responsible for the lack of patient adherence to treatment. The present work aimed at the development of polymeric nanoparticles as controlled release form of TAM in order to reduce possible toxicity front to healthy human cells system. The nanoparticles of poly (lactic acid) (PLA) containing citrate of tamoxifen (CTAM) were developed by the method of emulsification-solvent evaporation. An optimization procedure was performed by varying the type of surfactant (polyvinyl alcohol, polysorbate 80 or poloxamer 188) and the same concentrations (1 or 2%). The choice of the best formulation was based on features of lower mean diameter and higher encapsulation efficiency (EE%). The optimized formulation was used that 1% PVA, which had the following characteristics: 155.3 ± 4.11 nm and 85.18 ± 8.11% encapsulation of CTAM. The analysis of the drugpolymer interaction have shown that the process of nanoencapsulation generated amorphization CTAM conveyed to the nanoparticles. The in vitro release study demonstrated that CTAM has biphasic and controlled release from the nanoparticles with kinetic type of the second order coefficient Korsmeyer-Peppas indicated that the release mechanism is the diffusion-type CTAM. In the cell toxicity tests erythrocytes, nanoparticles containing CTAM showed no hemolytic potential, in contrast to free drug which showed high erythrocyte lysis. When evaluated the cytotoxicity on Hela tumor cell line, CTAM nanoencapsulado had lower cytotoxic than free CTAM, but maintained antitumor drug action. The results show that the nanoparticles have a potential for application as controlled release of antitumor treatments CTAM system.O tamoxifeno (TAM) é um fármaco amplamente utilizado como adjuvante na terapia do câncer de mama. Apesar de apresentar alta biodisponibilidade, apresenta elevados efeitos tóxicos, fato que pode ser responsável pela falta de adesão do paciente ao tratamento. O presente trabalho visou o desenvolvimento de nanopartículas poliméricas como forma de sistema de liberação controlada de TAM a fim de reduzir uma possível toxicidade frente às células humanas saudáveis. As nanopartículas de poli (ácido láctico) (PLA) contendo citrato de tamoxifeno (CTAM) foram desenvolvidas pelo método de emulsificação-evaporação do solvente. Foi realizada uma otimização do processo, variando o tipo de tensoativo (álcool polivinílico, polissorbato-80 ou poloxamer 188), bem como a concentração do mesmo (1 ou 2%), objetivando na escolha da melhor formulação perante as características de menor diâmetro médio e maior eficiência de encapsulação (EE%). A formulação otimizada, foi a que utilizou PVA a 1%, a qual apresentou as seguintes características: 155,3 ± 4,11 nm e 85,18 ± 8,11 % de encapsulação do CTAM. As análises de interação fármaco-polímero mostraram que o processo de nanoencapsulação gerou amorfização do CTAM veiculado às nanopartículas. O estudo de liberação in vitro, demonstrou que o CTAM apresenta liberação controlada e bifásica a partir das nanopartículas, com cinética do tipo de segunda ordem e o coeficiente de Korsmeyer-Peppas indicou que o mecanismo de liberação do CTAM é do tipo difusão. Nos testes de toxicidade celular sobre hemácias, as nanopartículas contendo CTAM não apresentaram potencial hemolítico, ao contrário do fármaco livre, que apresentou elevada lise eritrocitária. Quando avaliada a citotoxicidade sobre a linhagem tumoral Hela, o CTAM nanoencapsulado obteve menor ação citotóxica ao CTAM livre, porém manteve a ação antitumoral do fármaco. Os resultados demonstram que as nanopartículas apresentam potencial para aplicação como sistema de liberação controlada de CTAM em tratamentos antitumorais.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2017-06-01T19:31:22Z No. of bitstreams: 1 CLESCILA ALTMEYER.pdf: 914486 bytes, checksum: fc7d500868d01a768c3bdf1d591fae40 (MD5)Made available in DSpace on 2017-06-01T19:31:22Z (GMT). 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dc.title.por.fl_str_mv |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
title |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
spellingShingle |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS ALTMEYER, CLESCILA nanopartículas poli (ácido láctico) citotoxicidade câncer de mama tamoxifeno nanoparticles poly (lactic acid) cytotoxicity breast cancer tamoxifen CIENCIAS DA SAUDE::FARMACIA |
title_short |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
title_full |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
title_fullStr |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
title_full_unstemmed |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
title_sort |
OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS |
author |
ALTMEYER, CLESCILA |
author_facet |
ALTMEYER, CLESCILA |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Mainardes, Rubiana Mara |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7632867790178003 |
dc.contributor.advisor-co1.fl_str_mv |
Khalil, Najeh Maissar |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/8578241611510102 |
dc.contributor.authorID.fl_str_mv |
005.645.369-89 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2996620184791260 |
dc.contributor.author.fl_str_mv |
ALTMEYER, CLESCILA |
contributor_str_mv |
Mainardes, Rubiana Mara Khalil, Najeh Maissar |
dc.subject.por.fl_str_mv |
nanopartículas poli (ácido láctico) citotoxicidade câncer de mama tamoxifeno nanoparticles poly (lactic acid) cytotoxicity breast cancer tamoxifen |
topic |
nanopartículas poli (ácido láctico) citotoxicidade câncer de mama tamoxifeno nanoparticles poly (lactic acid) cytotoxicity breast cancer tamoxifen CIENCIAS DA SAUDE::FARMACIA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
description |
Tamoxifen (TAM) is a drug widely used as an adjuvant in breast cancer therapy. Despite showing high bioavailability, has high toxicity, which may be responsible for the lack of patient adherence to treatment. The present work aimed at the development of polymeric nanoparticles as controlled release form of TAM in order to reduce possible toxicity front to healthy human cells system. The nanoparticles of poly (lactic acid) (PLA) containing citrate of tamoxifen (CTAM) were developed by the method of emulsification-solvent evaporation. An optimization procedure was performed by varying the type of surfactant (polyvinyl alcohol, polysorbate 80 or poloxamer 188) and the same concentrations (1 or 2%). The choice of the best formulation was based on features of lower mean diameter and higher encapsulation efficiency (EE%). The optimized formulation was used that 1% PVA, which had the following characteristics: 155.3 ± 4.11 nm and 85.18 ± 8.11% encapsulation of CTAM. The analysis of the drugpolymer interaction have shown that the process of nanoencapsulation generated amorphization CTAM conveyed to the nanoparticles. The in vitro release study demonstrated that CTAM has biphasic and controlled release from the nanoparticles with kinetic type of the second order coefficient Korsmeyer-Peppas indicated that the release mechanism is the diffusion-type CTAM. In the cell toxicity tests erythrocytes, nanoparticles containing CTAM showed no hemolytic potential, in contrast to free drug which showed high erythrocyte lysis. When evaluated the cytotoxicity on Hela tumor cell line, CTAM nanoencapsulado had lower cytotoxic than free CTAM, but maintained antitumor drug action. The results show that the nanoparticles have a potential for application as controlled release of antitumor treatments CTAM system. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-08-08 |
dc.date.accessioned.fl_str_mv |
2017-06-01T19:31:22Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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dc.identifier.citation.fl_str_mv |
ALTMEYER, CLESCILA. OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS. 2014. 90 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR. |
dc.identifier.uri.fl_str_mv |
http://tede.unicentro.br:8080/jspui/handle/jspui/660 |
identifier_str_mv |
ALTMEYER, CLESCILA. OBTENÇÃO DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO TAMOXIFENO E AVALIAÇÃO DA CITOTOXICIDADE SOBRE HEMÁCIAS E CÉLULAS TUMORAIS. 2014. 90 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR. |
url |
http://tede.unicentro.br:8080/jspui/handle/jspui/660 |
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por |
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por |
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6997636413449754996 |
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openAccess |
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Universidade Estadual do Centro-Oeste |
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UNICENTRO |
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Brasil |
dc.publisher.department.fl_str_mv |
Unicentro::Departamento de Farmácia |
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Universidade Estadual do Centro-Oeste |
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