OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/684 |
Resumo: | Ursolic acid (UA) is a pentacyclic triterpenoid present in many food and medicinal species, which was consecrated due to its antioxidant action, and currently has expanded its research due to its ability to inhibit various stages in the development of tumors. However, its clinical application is limited due to its low aqueous solubility, which results in low oral bioavailability, restricting its effectiveness. In an attempt to overcome these limitations, the present work developed nanoparticles of poly (lactic acid) (PLA) containing UA through the method of emulsification-solvent evaporation. In order to obtain a tool able to quantify the UA present in nanoparticles, an analytical method using high-performance liquid chromatography (HPLC) coupled to a photodiode detector array (PDA) was developed and validated in accordance with current norms. PLA nanoparticles containing UA were successfully obtained and presented an encapsulation efficiency of 96%, and 246 nm in mean size, with spherical or slightly oval morphology. Zeta potential of the formulation was -24,6 mV, a value which ensures a good physicochemical stability. The spectroscopic in infrared, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis suggests interaction/complexation of UA with the polymeric matrix and amorphization of the drug promoted by nanoencapsulation process. Stability study showed that the best condition for storage of NP's was at room temperature, since in this condition all parameters were stable for 6 months. The in vitro release study showed that UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. At the end of 120 h about 60% of the encapsulated UA was released by diffusion. In cytotoxicity test front red blood cells, it was observed that the NP's containing UA showed less toxicity on cells than free drug. When evaluated the cytotoxicity over tumor cells line B16 -F10, UA nanoencapsulated keeped the antitumor capacity of the drug. By studying the antioxidant activity via inhibition of hypochlorous acid, it was observed that the nanoencapsulation process does not influence the UA antioxidant capacity, whereas after 72 h, the NP's presented inhibition capacity similar to free UA. Thus, it is concluded that NP's containing UA developed in this study had adequate physic chemical characteristics, which make them potential drug delivery systems while maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity on normal cells. |
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Mainardes, Rubiana Marahttp://lattes.cnpq.br/7632867790178003081.506.619-80http://lattes.cnpq.br/4391061802919621ANTÔNIO, EMILLI2017-06-09T13:09:10Z2016-02-23ANTÔNIO, EMILLI. OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO. 2016. 129 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/684Ursolic acid (UA) is a pentacyclic triterpenoid present in many food and medicinal species, which was consecrated due to its antioxidant action, and currently has expanded its research due to its ability to inhibit various stages in the development of tumors. However, its clinical application is limited due to its low aqueous solubility, which results in low oral bioavailability, restricting its effectiveness. In an attempt to overcome these limitations, the present work developed nanoparticles of poly (lactic acid) (PLA) containing UA through the method of emulsification-solvent evaporation. In order to obtain a tool able to quantify the UA present in nanoparticles, an analytical method using high-performance liquid chromatography (HPLC) coupled to a photodiode detector array (PDA) was developed and validated in accordance with current norms. PLA nanoparticles containing UA were successfully obtained and presented an encapsulation efficiency of 96%, and 246 nm in mean size, with spherical or slightly oval morphology. Zeta potential of the formulation was -24,6 mV, a value which ensures a good physicochemical stability. The spectroscopic in infrared, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis suggests interaction/complexation of UA with the polymeric matrix and amorphization of the drug promoted by nanoencapsulation process. Stability study showed that the best condition for storage of NP's was at room temperature, since in this condition all parameters were stable for 6 months. The in vitro release study showed that UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. At the end of 120 h about 60% of the encapsulated UA was released by diffusion. In cytotoxicity test front red blood cells, it was observed that the NP's containing UA showed less toxicity on cells than free drug. When evaluated the cytotoxicity over tumor cells line B16 -F10, UA nanoencapsulated keeped the antitumor capacity of the drug. By studying the antioxidant activity via inhibition of hypochlorous acid, it was observed that the nanoencapsulation process does not influence the UA antioxidant capacity, whereas after 72 h, the NP's presented inhibition capacity similar to free UA. Thus, it is concluded that NP's containing UA developed in this study had adequate physic chemical characteristics, which make them potential drug delivery systems while maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity on normal cells.O ácido ursólico (AU) é um triterpenoide pentacíclico presente em diversas espécies alimentícias e medicinais, que se destacou devido à sua ação antioxidante, e atualmente ampliou-se sua pesquisa devido sua capacidade de inibir diversos estágios no desenvolvimento de tumores. No entanto, sua aplicação clínica é limitada devido à sua baixa solubilidade aquosa, que resulta em baixa biodisponibilidade oral e restringe sua eficácia. Na tentativa de vencer essas limitações, no presente trabalho desenvolveu-se nanopartículas poliméricas (NP’s) à base de poli (ácido láctico) (PLA) contendo AU através do método da emulsificação-evaporação do solvente. A fim de se obter uma ferramenta capaz de quantificar o AU presente nas nanopartículas, um método analítico utilizando cromatografia líquida de alta eficiência (CLAE) acoplada a um detector de arranjo de diodos (DAD) foi desenvolvido e validado de acordo com as normatizações vigentes. As NP’s de PLA contendo AU foram obtidas com êxito e apresentaram eficiência de encapsulação de 96% e diâmetro médio de 246 nm, com morfologia esférica ou levemente ovalada. O potencial zeta da formulação foi de -24,6 mV, valor que garante uma boa estabilidade físico-química. As análises de espectroscopia no infravermelho, difração de raios X, calorimetria exploratória diferencial e termogravimetria sugerem a interação/complexação do AU com a matriz polimérica e amorfização do fármaco, promovidas pelo processo de nanoencapsulação. O estudo de estabilidade revelou que a melhor condição para armazenamento das NP’s foi à temperatura ambiente, já que nessas condições todos os parâmetros analisados se mostraram estáveis durante 6 meses. O estudo de liberação in vitro mostrou que o AU foi liberado da matriz polimérica através de 2 constantes (α, β), sugerindo uma cinética de segunda ordem. Ao final de 120 h cerca de 60% de AU encapsulado foi liberado por meio de difusão. No teste de citotoxicidade frente a hemácias, foi possível verificar que as NP’s contendo AU apresentaram menor toxicidade sobre as células do que o fármaco livre. Quando avaliada a citotoxicidade sobre a linhagem tumoral B16-F10, o AU nanoencapsulado demonstrou manter a capacidade antitumoral do fármaco. Através do estudo do potencial antioxidante via inibição do ácido hipocloroso, observou-se que o processo de nanoencapsulação não influenciou na capacidade antioxidante do AU, visto que após 72 h, as NP’s apresentaram capacidade de inibição semelhante ao AU livre. Assim, conclui-se que as NP’s contendo AU desenvolvidas neste estudo apresentam características físico-químicas adequadas, o que as tornam potenciais sistemas de liberação controlada, mantendo a atividade antioxidante e antitumoral do AU e diminuindo sua citotoxicidade sobre células normais.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2017-06-09T13:09:10Z No. of bitstreams: 1 EMILLI ANTÔNIO.pdf: 2658339 bytes, checksum: d76efeb2893f6fca5a8864e7328cb407 (MD5)Made available in DSpace on 2017-06-09T13:09:10Z (GMT). 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dc.title.por.fl_str_mv |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
title |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
spellingShingle |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO ANTÔNIO, EMILLI nanopartículas citotoxicidade antioxidante estabilidade poli(ácido láctico) ácido ursólico nanoparticles citotoxicity antioxidant stability poly (lactic acid) ursolic acid CIENCIAS DA SAUDE::FARMACIA |
title_short |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
title_full |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
title_fullStr |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
title_full_unstemmed |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
title_sort |
OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO |
author |
ANTÔNIO, EMILLI |
author_facet |
ANTÔNIO, EMILLI |
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.authorID.fl_str_mv |
081.506.619-80 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4391061802919621 |
dc.contributor.author.fl_str_mv |
ANTÔNIO, EMILLI |
contributor_str_mv |
Mainardes, Rubiana Mara |
dc.subject.por.fl_str_mv |
nanopartículas citotoxicidade antioxidante estabilidade poli(ácido láctico) ácido ursólico |
topic |
nanopartículas citotoxicidade antioxidante estabilidade poli(ácido láctico) ácido ursólico nanoparticles citotoxicity antioxidant stability poly (lactic acid) ursolic acid CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
nanoparticles citotoxicity antioxidant stability poly (lactic acid) ursolic acid |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::FARMACIA |
description |
Ursolic acid (UA) is a pentacyclic triterpenoid present in many food and medicinal species, which was consecrated due to its antioxidant action, and currently has expanded its research due to its ability to inhibit various stages in the development of tumors. However, its clinical application is limited due to its low aqueous solubility, which results in low oral bioavailability, restricting its effectiveness. In an attempt to overcome these limitations, the present work developed nanoparticles of poly (lactic acid) (PLA) containing UA through the method of emulsification-solvent evaporation. In order to obtain a tool able to quantify the UA present in nanoparticles, an analytical method using high-performance liquid chromatography (HPLC) coupled to a photodiode detector array (PDA) was developed and validated in accordance with current norms. PLA nanoparticles containing UA were successfully obtained and presented an encapsulation efficiency of 96%, and 246 nm in mean size, with spherical or slightly oval morphology. Zeta potential of the formulation was -24,6 mV, a value which ensures a good physicochemical stability. The spectroscopic in infrared, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis suggests interaction/complexation of UA with the polymeric matrix and amorphization of the drug promoted by nanoencapsulation process. Stability study showed that the best condition for storage of NP's was at room temperature, since in this condition all parameters were stable for 6 months. The in vitro release study showed that UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. At the end of 120 h about 60% of the encapsulated UA was released by diffusion. In cytotoxicity test front red blood cells, it was observed that the NP's containing UA showed less toxicity on cells than free drug. When evaluated the cytotoxicity over tumor cells line B16 -F10, UA nanoencapsulated keeped the antitumor capacity of the drug. By studying the antioxidant activity via inhibition of hypochlorous acid, it was observed that the nanoencapsulation process does not influence the UA antioxidant capacity, whereas after 72 h, the NP's presented inhibition capacity similar to free UA. Thus, it is concluded that NP's containing UA developed in this study had adequate physic chemical characteristics, which make them potential drug delivery systems while maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity on normal cells. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-02-23 |
dc.date.accessioned.fl_str_mv |
2017-06-09T13:09:10Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ANTÔNIO, EMILLI. OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO. 2016. 129 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/684 |
identifier_str_mv |
ANTÔNIO, EMILLI. OBTENÇÃO, CARACTERIZAÇÃO E AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E CITOTÓXICA DE NANOPARTÍCULAS DE POLI (ÁCIDO LÁCTICO) CONTENDO ÁCIDO URSÓLICO. 2016. 129 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/684 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
-7679163762264962259 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
-6934766838009717290 |
dc.relation.cnpq.fl_str_mv |
6997636413449754996 |
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 Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG) |
dc.publisher.initials.fl_str_mv |
UNICENTRO |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Unicentro::Departamento de Farmácia |
publisher.none.fl_str_mv |
Universidade Estadual do Centro-Oeste |
dc.source.none.fl_str_mv |
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Universidade Estadual do Centro-Oeste (UNICENTRO) |
instacron_str |
UNICENTRO |
institution |
UNICENTRO |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UNICENTRO |
collection |
Biblioteca Digital de Teses e Dissertações do UNICENTRO |
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MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UNICENTRO - Universidade Estadual do Centro-Oeste (UNICENTRO) |
repository.mail.fl_str_mv |
repositorio@unicentro.br||fabianoqueiroz@yahoo.com.br |
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1811733811476561920 |