Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade
Ano de defesa: | 2019 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Estadual do Centro-Oeste
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química (Doutorado)
|
Departamento: |
Unicentro::Departamento de Ciências Exatas e de Tecnologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede.unicentro.br:8080/jspui/handle/jspui/1584 |
Resumo: | Systemic fungal infections consist of the leading causes of mortality among hospitalized immunocompromised patients. Amphotericin B (AmB) is the drug of choice in these situations because it is a broad spectrum antifungal. Despite its effectiveness, AmB is used only through parenteral route, as it has low oral bioavailability, as well as renal cell toxicity. It also has activity on the immune system and ability to form reactive oxygen species (ROS), which assists in antifungal activity but also in the toxicity of the molecule. In this study, chitosan-coated (poly-lactic-co-glycolic) acid (PLGA) nanoparticles containing AmB were developed and evaluated for oral application. The choice of polymers was due to the biocompatibility and the mucoadhesive characteristics of chitosan. The nanoparticles were developed by the emulsion-solvent evaporation method and had a mean diameter of 204 ± 22 nm, a polydispersion index of 0.197 ± 0.01 and an encapsulation efficiency of 93.3 ± 0.4 %. The zeta potential of +21 ± 0.8 mV was compatible with the presence of chitosan on the surface. The results of X-ray diffraction studies and thermal analysis demonstrated amorphization of AmB after nanoencapsulation and consequently an improvement in stability of the molecule. The in vitro release profile was prolonged and biphasic, releasing 56 % of AmB after 120h. The nanoparticles were stable in simulated gastric and intestinal media, promoting an AmB release of 0.2 % and 1.4 %, respectively. In the results of the in vitro determination of the mucoadhesive capacity it was observed that the chitosan promoted the interaction of the nanoparticles with mucin. The nanoparticles reduced significantly the AmB cytotoxicity on erythrocytes and Vero cells demonstrating compatibility with the results obtained in the aggregation assay, where AmB released from the system prevails in the monomeric state, that is, more soluble and less toxic form. The in vitro assay of antifungal efficacy on strains of Candida spp. and Trichosporon spp. showed the action of the nanoparticles containing AmB in reducing the amount of fungal colony forming units (CFU) by determining the minimum inhibitory concentration (MIC) compared to the free AmB. Thus, AmB chitosan-coated PLGA nanoparticles are promising alternative for the treatment of systemic fungal infections by the oral route. |
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Mainardes, Rubiana Marahttp://lattes.cnpq.br/7632867790178003Khalil, Najeh Maissarhttp://lattes.cnpq.br/8578241611510102030.300.419-30http://lattes.cnpq.br/1251892758640312Ludwig, Daniel Brustolin2021-04-30T13:22:51Z2019-02-28Ludwig, Daniel Brustolin. Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade. 2019. 104 f. Tese (Programa de Pós-Graduação em Química - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.http://tede.unicentro.br:8080/jspui/handle/jspui/1584Systemic fungal infections consist of the leading causes of mortality among hospitalized immunocompromised patients. Amphotericin B (AmB) is the drug of choice in these situations because it is a broad spectrum antifungal. Despite its effectiveness, AmB is used only through parenteral route, as it has low oral bioavailability, as well as renal cell toxicity. It also has activity on the immune system and ability to form reactive oxygen species (ROS), which assists in antifungal activity but also in the toxicity of the molecule. In this study, chitosan-coated (poly-lactic-co-glycolic) acid (PLGA) nanoparticles containing AmB were developed and evaluated for oral application. The choice of polymers was due to the biocompatibility and the mucoadhesive characteristics of chitosan. The nanoparticles were developed by the emulsion-solvent evaporation method and had a mean diameter of 204 ± 22 nm, a polydispersion index of 0.197 ± 0.01 and an encapsulation efficiency of 93.3 ± 0.4 %. The zeta potential of +21 ± 0.8 mV was compatible with the presence of chitosan on the surface. The results of X-ray diffraction studies and thermal analysis demonstrated amorphization of AmB after nanoencapsulation and consequently an improvement in stability of the molecule. The in vitro release profile was prolonged and biphasic, releasing 56 % of AmB after 120h. The nanoparticles were stable in simulated gastric and intestinal media, promoting an AmB release of 0.2 % and 1.4 %, respectively. In the results of the in vitro determination of the mucoadhesive capacity it was observed that the chitosan promoted the interaction of the nanoparticles with mucin. The nanoparticles reduced significantly the AmB cytotoxicity on erythrocytes and Vero cells demonstrating compatibility with the results obtained in the aggregation assay, where AmB released from the system prevails in the monomeric state, that is, more soluble and less toxic form. The in vitro assay of antifungal efficacy on strains of Candida spp. and Trichosporon spp. showed the action of the nanoparticles containing AmB in reducing the amount of fungal colony forming units (CFU) by determining the minimum inhibitory concentration (MIC) compared to the free AmB. Thus, AmB chitosan-coated PLGA nanoparticles are promising alternative for the treatment of systemic fungal infections by the oral route.As infecções fúngicas sistêmicas estão entre as principais causas de mortalidade entre pacientes imunocomprometidos internados. A anfotericina B (AFB) é o fármaco de escolha nessas situações, pois é um antifúngico de amplo espectro. Apesar de sua eficácia, a AFB é utilizada somente pela via parenteral, pois apresenta baixa biodisponibilidade pela via oral, bem como apresenta toxicidade às células renais. Também possui atividade sobre o sistema imunológico e capacidade de formação de espécies reativas de oxigênio (EROs), o que auxilia na atividade antifúngica mas também na toxicidade da molécula. Neste estudo, nanopartículas de ácido(poli-lático-co-glicólico) (PLGA) revestidas com quitosana contendo AFB foram desenvolvidas e avaliadas para futura aplicação pela via oral. A escolha dos polímeros deu-se pela biocompatibilidade e pelas características mucoadesivas da quitosana. As nanopartículas foram desenvolvidas pela técnica de emulsificação-evaporação do solvente e apresentaram diâmetro médio de 204 ± 22 nm, índice de polidispersão de 0,197 ± 0,01 e eficiência de encapsulação de 93,3 ± 0,4 %. O potencial zeta de +21 ± 0,8 mV foi compatível com a presença da quitosana na superfície. Os resultados dos estudos de difração de raios x e a análise térmica demonstraram a amorfização da AFB após nanoencapsulação e consequentemente uma melhora na estabilidade da molécula. O perfil de liberação in vitro mostrou-se prolongado e bifásico, liberando 56 % da AFB após as 120h. As nanopartículas foram estáveis em meios gástrico e intestinal simulados, promovendo a liberação de 0,2 % e 1,4 % de AFB, respectivamente. Nos resultados da determinação in vitro da capacidade mucoadesiva observou-se que a quitosana promoveu a interação das nanopartículas com a mucina. As nanopartículas reduziram significativamente a citotoxicidade da AFB sobre eritrócitos e células Vero demonstrando compatibilidade com os resultados obtidos no ensaio de agregação, onde a AFB liberada do sistema prevalece na forma monomérica, ou seja, mais solúvel e menos tóxica. O ensaio in vitro de eficácia antifúngica sobre cepas de Candida spp. e Trichosporon spp. mostrou a ação das nanopartículas contendo AFB na redução da quantidade de unidades formadoras de colônias (UFC) dos fungos através da determinação da concentração inibitória mínima (CIM) em comparação com a AFB livre. Desta forma, as nanopartículas de PLGA revestidas com quitosana contendo AFB são promissoras alternativas para o tratamento de infecções fúngicas sistêmicas pela via oral.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2021-04-30T13:22:51Z No. of bitstreams: 1 Tese DANIEL BRUSTOLIN LUDWIG.pdf: 1985295 bytes, checksum: 0b8b34fd2d44575859472cbe972666d3 (MD5)Made available in DSpace on 2021-04-30T13:22:51Z (GMT). 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dc.title.por.fl_str_mv |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
title |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
spellingShingle |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade Ludwig, Daniel Brustolin Anfotericina B Quitosana Nanopartículas Mucoadesão Antifúngico Células Vero Amphotericin B Chitosan Nanoparticles Mucoadhesion Antifungal Vero cells CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
title_full |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
title_fullStr |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
title_full_unstemmed |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
title_sort |
Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade |
author |
Ludwig, Daniel Brustolin |
author_facet |
Ludwig, Daniel Brustolin |
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 |
030.300.419-30 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1251892758640312 |
dc.contributor.author.fl_str_mv |
Ludwig, Daniel Brustolin |
contributor_str_mv |
Mainardes, Rubiana Mara Khalil, Najeh Maissar |
dc.subject.por.fl_str_mv |
Anfotericina B Quitosana Nanopartículas Mucoadesão Antifúngico Células Vero |
topic |
Anfotericina B Quitosana Nanopartículas Mucoadesão Antifúngico Células Vero Amphotericin B Chitosan Nanoparticles Mucoadhesion Antifungal Vero cells CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Amphotericin B Chitosan Nanoparticles Mucoadhesion Antifungal Vero cells |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Systemic fungal infections consist of the leading causes of mortality among hospitalized immunocompromised patients. Amphotericin B (AmB) is the drug of choice in these situations because it is a broad spectrum antifungal. Despite its effectiveness, AmB is used only through parenteral route, as it has low oral bioavailability, as well as renal cell toxicity. It also has activity on the immune system and ability to form reactive oxygen species (ROS), which assists in antifungal activity but also in the toxicity of the molecule. In this study, chitosan-coated (poly-lactic-co-glycolic) acid (PLGA) nanoparticles containing AmB were developed and evaluated for oral application. The choice of polymers was due to the biocompatibility and the mucoadhesive characteristics of chitosan. The nanoparticles were developed by the emulsion-solvent evaporation method and had a mean diameter of 204 ± 22 nm, a polydispersion index of 0.197 ± 0.01 and an encapsulation efficiency of 93.3 ± 0.4 %. The zeta potential of +21 ± 0.8 mV was compatible with the presence of chitosan on the surface. The results of X-ray diffraction studies and thermal analysis demonstrated amorphization of AmB after nanoencapsulation and consequently an improvement in stability of the molecule. The in vitro release profile was prolonged and biphasic, releasing 56 % of AmB after 120h. The nanoparticles were stable in simulated gastric and intestinal media, promoting an AmB release of 0.2 % and 1.4 %, respectively. In the results of the in vitro determination of the mucoadhesive capacity it was observed that the chitosan promoted the interaction of the nanoparticles with mucin. The nanoparticles reduced significantly the AmB cytotoxicity on erythrocytes and Vero cells demonstrating compatibility with the results obtained in the aggregation assay, where AmB released from the system prevails in the monomeric state, that is, more soluble and less toxic form. The in vitro assay of antifungal efficacy on strains of Candida spp. and Trichosporon spp. showed the action of the nanoparticles containing AmB in reducing the amount of fungal colony forming units (CFU) by determining the minimum inhibitory concentration (MIC) compared to the free AmB. Thus, AmB chitosan-coated PLGA nanoparticles are promising alternative for the treatment of systemic fungal infections by the oral route. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-02-28 |
dc.date.accessioned.fl_str_mv |
2021-04-30T13:22:51Z |
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 |
Ludwig, Daniel Brustolin. Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade. 2019. 104 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/1584 |
identifier_str_mv |
Ludwig, Daniel Brustolin. Nanopartículas de poli(ácido láctico-co-glicólico) revestidas com quitosana contendo anfotericina B: desenvolvimento, caracterização e avaliação in vitro da eficácia e toxicidade. 2019. 104 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/1584 |
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 |
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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 |
reponame:Biblioteca Digital de Teses e Dissertações do UNICENTRO instname:Universidade Estadual do Centro-Oeste (UNICENTRO) instacron:UNICENTRO |
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Universidade Estadual do Centro-Oeste (UNICENTRO) |
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UNICENTRO |
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UNICENTRO |
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Biblioteca Digital de Teses e Dissertações do UNICENTRO |
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Biblioteca Digital de Teses e Dissertações do UNICENTRO |
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MD5 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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1796502102029107200 |