PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS

Detalhes bibliográficos
Autor(a) principal: Possani, Liliane Medianeira Mayer
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional Universidade Franciscana
Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/540
Resumo: Herpes is a condition caused by Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) which largely affects the global population. Both species can be transmitted through direct contact with infected lesions or biological fluids such as saliva and genital fluids. However, asymptomatic carriers can also transmit and excrete virus. Control of herpes is accomplished through the use of antiviral drugs, however, its extensive use has led to the emergence of resistant virus strains, particularly in immunocompromised patients. Because of that the development of an effective vaccine will not only control the disease, but also its etiologic agent. HSV-1 is an enveloped DNA viruses, and in this envelope there are viral glycoproteins that are responsible for the process of entering into the host cell. The mainly glycoproteins are B (gB) glycoprotein D (gD), glycoprotein H (gH) and glycoprotein L (gL). Glycoprotein B is the most studied protein and the reason for that is because its sequence is conserved among all herpesviruses and also is essential for the cell infection process. In this glycoprotein there is a fragment of 8 amino acid residues referred SSIEFARL. It is an immunodominant peptide responsible for inducing a strong T cell response upon infection process. This peptide is poorly immunogenic when adminstered without protection and or adjuvant. Thus, the nanobiotechnology can help for the development of a potent adjuvant to protect SSIEFARL and increase its immunogenicity. For this propouse, the production of previous developed polymeric nanocapsules (NCPs) with aqueous core was otimized and its physical and chemical parameters determined. After otimization, the encapsulation efficiency of SSIEFARL was evaluated and the interaction/compatibility of unloaded NCPs with cell in vitro were also determined. The NCPs presented unimodal distribution, low PDI (0.23±0.03), mean diameter of 267.5±51.6 and zeta potential -29.6±2.2, pH 7.2±0.3. The analyzes showed that 98% (97.7±1.5) of the particles in the sample were in the nanoscale and the a concentration of NCPs 6,07x1010/cm3. In vitro tests showed no cytotoxicity, and unload NCPs and in vivo tested suggest a cell migration to the site of injection and draning to the reagional lymph nodes, suggesting some adjuvant propertie. Taken together, the data suggest that the NCPs can be used in the development of an adjuvant system for the protection of SSIEFARL and development of a vaccine against HSV-1.
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spelling Rodrigues Junior, Luiz CarlosTsao, MarisaFagan, Solange BinottoPossani, Liliane Medianeira Mayer2018-08-16T20:02:22Z2015-03-26Possani, Liliane Medianeira Mayer. PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS. 2015. 71f. Dissertação( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/540Herpes is a condition caused by Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) which largely affects the global population. Both species can be transmitted through direct contact with infected lesions or biological fluids such as saliva and genital fluids. However, asymptomatic carriers can also transmit and excrete virus. Control of herpes is accomplished through the use of antiviral drugs, however, its extensive use has led to the emergence of resistant virus strains, particularly in immunocompromised patients. Because of that the development of an effective vaccine will not only control the disease, but also its etiologic agent. HSV-1 is an enveloped DNA viruses, and in this envelope there are viral glycoproteins that are responsible for the process of entering into the host cell. The mainly glycoproteins are B (gB) glycoprotein D (gD), glycoprotein H (gH) and glycoprotein L (gL). Glycoprotein B is the most studied protein and the reason for that is because its sequence is conserved among all herpesviruses and also is essential for the cell infection process. In this glycoprotein there is a fragment of 8 amino acid residues referred SSIEFARL. It is an immunodominant peptide responsible for inducing a strong T cell response upon infection process. This peptide is poorly immunogenic when adminstered without protection and or adjuvant. Thus, the nanobiotechnology can help for the development of a potent adjuvant to protect SSIEFARL and increase its immunogenicity. For this propouse, the production of previous developed polymeric nanocapsules (NCPs) with aqueous core was otimized and its physical and chemical parameters determined. After otimization, the encapsulation efficiency of SSIEFARL was evaluated and the interaction/compatibility of unloaded NCPs with cell in vitro were also determined. The NCPs presented unimodal distribution, low PDI (0.23±0.03), mean diameter of 267.5±51.6 and zeta potential -29.6±2.2, pH 7.2±0.3. The analyzes showed that 98% (97.7±1.5) of the particles in the sample were in the nanoscale and the a concentration of NCPs 6,07x1010/cm3. In vitro tests showed no cytotoxicity, and unload NCPs and in vivo tested suggest a cell migration to the site of injection and draning to the reagional lymph nodes, suggesting some adjuvant propertie. Taken together, the data suggest that the NCPs can be used in the development of an adjuvant system for the protection of SSIEFARL and development of a vaccine against HSV-1.A herpes é uma patologia causada pelo Herpes Simplex Vírus dos tipos 1 (HSV-1) e 2 (HSV-2) que afeta grande parte da população mundial. Ambas as espécies podem ser transmitidas através de contato direto com lesões ou fluidos biológicos infectados, como saliva e fluidos genitais. No entanto, portadores assintomáticos também podem excretar e transmitir os vírus. O controle da herpes é realizado através do uso de medicamentos antivirais, porém seu uso extensivo, levou ao aparecimento de linhagens de vírus resistentes, principalmente em pacientes imunocomprometidos. Esse fato torna imprescindível o desenvolvimento de uma vacina que seja eficaz não só no controle da doença, mas também de seu agente etiológico. O HSV-1 é um vírus de DNA envelopado e, nesse envelope estão ancoradas glicoproteínas virais que são responsáveis pelo processo de entrada na célula hospedeira, sendo as principais glicoproteína B (gB), glicoproteína D (gD), glicoproteína H (gH) e glicoproteína L (gL). A gB é um dos principais alvos nas pesquisas por ser uma sequência conservada em todos os herpesvírus e essencial no processo de infecção da célula alvo. Nessa glicoproteína, há um fragmento constituído por 8 resíduos de aminoácidos denominado SSIEFARL. Trata-se de um peptídeo imunodominante responsável por induzir forte resposta de células T no processo de infecção. Porém, esse peptídeo, quando administrado livre, é fracamente imunogênico. Sendo assim, busca-se na nanobiotecnologia, o desenvolvimento de um adjuvante potente para proteger o peptídeo e aumentar sua imunogenicidade. Para isso, nanocápsulas poliméricas (NCPs) de núcleo aquoso previamente desenvolvidas, tiveram sua produção otimizada e seus parâmetros físico-químicos avaliados. Após o estabelecimento das condições ótimas de produção, foram analisados o encapsulamento do SSIEFARL e testes para verificar a interação das NCPs brancas com cultura celular. As NCPs apresentaram distribuição unimodal, baixo PDI (0,23 ± 0,03), diâmetro médio de 267,5±51,6 e potencial zeta -29,6±2,2, com pH 7,2±0,3. As análises mostraram que aproximadamente 98% (97,7±1,5) das partículas presentes na amostra estão na escala nanométrica em uma concentração de 6,07x1010 NCPs/cm3. Os testes in vitro não evidenciaram citotoxicidade, e as NCPs brancas apresentaram capacidade de induzir migração celular ao local da injeção com tendência à drenagem dessas células aos linfonodos, sugerindo bom efeito adjuvante. A partir desses resultados pode-se sugerir que as NCPs podem ser utilizadas no desenvolvimento de um sistema adjuvante para a proteção do SSIEFARL e desenvolvimento de uma vacina contra o HSV-1.Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-16T20:02:22Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_LilianeMedianeiraMayerPossani.pdf: 1773175 bytes, checksum: 0fea418092d5f10f54b9e5790226b20b (MD5)Made available in DSpace on 2018-08-16T20:02:22Z (GMT). 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dc.title.por.fl_str_mv PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
title PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
spellingShingle PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
Possani, Liliane Medianeira Mayer
Herpes; HSV-1; SSIEFARL; Nanovacinas.
Herpes; HSV-1; SSIEFARL; Nanovaccines.
Biociências e Nanomateriais
title_short PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
title_full PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
title_fullStr PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
title_full_unstemmed PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
title_sort PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS
author Possani, Liliane Medianeira Mayer
author_facet Possani, Liliane Medianeira Mayer
author_role author
dc.contributor.advisor1.fl_str_mv Rodrigues Junior, Luiz Carlos
dc.contributor.referee1.fl_str_mv Tsao, Marisa
dc.contributor.referee2.fl_str_mv Fagan, Solange Binotto
dc.contributor.author.fl_str_mv Possani, Liliane Medianeira Mayer
contributor_str_mv Rodrigues Junior, Luiz Carlos
Tsao, Marisa
Fagan, Solange Binotto
dc.subject.por.fl_str_mv Herpes; HSV-1; SSIEFARL; Nanovacinas.
topic Herpes; HSV-1; SSIEFARL; Nanovacinas.
Herpes; HSV-1; SSIEFARL; Nanovaccines.
Biociências e Nanomateriais
dc.subject.eng.fl_str_mv Herpes; HSV-1; SSIEFARL; Nanovaccines.
dc.subject.cnpq.fl_str_mv Biociências e Nanomateriais
description Herpes is a condition caused by Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) which largely affects the global population. Both species can be transmitted through direct contact with infected lesions or biological fluids such as saliva and genital fluids. However, asymptomatic carriers can also transmit and excrete virus. Control of herpes is accomplished through the use of antiviral drugs, however, its extensive use has led to the emergence of resistant virus strains, particularly in immunocompromised patients. Because of that the development of an effective vaccine will not only control the disease, but also its etiologic agent. HSV-1 is an enveloped DNA viruses, and in this envelope there are viral glycoproteins that are responsible for the process of entering into the host cell. The mainly glycoproteins are B (gB) glycoprotein D (gD), glycoprotein H (gH) and glycoprotein L (gL). Glycoprotein B is the most studied protein and the reason for that is because its sequence is conserved among all herpesviruses and also is essential for the cell infection process. In this glycoprotein there is a fragment of 8 amino acid residues referred SSIEFARL. It is an immunodominant peptide responsible for inducing a strong T cell response upon infection process. This peptide is poorly immunogenic when adminstered without protection and or adjuvant. Thus, the nanobiotechnology can help for the development of a potent adjuvant to protect SSIEFARL and increase its immunogenicity. For this propouse, the production of previous developed polymeric nanocapsules (NCPs) with aqueous core was otimized and its physical and chemical parameters determined. After otimization, the encapsulation efficiency of SSIEFARL was evaluated and the interaction/compatibility of unloaded NCPs with cell in vitro were also determined. The NCPs presented unimodal distribution, low PDI (0.23±0.03), mean diameter of 267.5±51.6 and zeta potential -29.6±2.2, pH 7.2±0.3. The analyzes showed that 98% (97.7±1.5) of the particles in the sample were in the nanoscale and the a concentration of NCPs 6,07x1010/cm3. In vitro tests showed no cytotoxicity, and unload NCPs and in vivo tested suggest a cell migration to the site of injection and draning to the reagional lymph nodes, suggesting some adjuvant propertie. Taken together, the data suggest that the NCPs can be used in the development of an adjuvant system for the protection of SSIEFARL and development of a vaccine against HSV-1.
publishDate 2015
dc.date.issued.fl_str_mv 2015-03-26
dc.date.accessioned.fl_str_mv 2018-08-16T20:02:22Z
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dc.identifier.citation.fl_str_mv Possani, Liliane Medianeira Mayer. PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS. 2015. 71f. Dissertação( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .
dc.identifier.uri.fl_str_mv http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/540
identifier_str_mv Possani, Liliane Medianeira Mayer. PRODUÇÃO E ANÁLISE DOS EFEITOS IMUNOBIOLÓGICOS DE NANOCÁPSULAS POLIMÉRICAS DE NÚCLEO AQUOSO SOBRE CÉLULAS DENDRÍTICAS MURINAS. 2015. 71f. Dissertação( Programa de Pós-Graduação em Nanociências) - Centro Universitário Franciscano, Santa Maria - RS .
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