Detalhes bibliográficos
| Ano de defesa: |
2019 |
| Autor(a) principal: |
Viana, Iara Maíra de Oliveira
 |
| Orientador(a): |
Lima, Eliana Martins
|
| Banca de defesa: |
Lima, Eliana Martins,
Guterres , Sílvia Stanisçuaski,
Zucolotto, Valtencir,
Valadares, Marize Campos,
Bakuzis, Andris Figueiroa |
| Tipo de documento: |
Tese
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
eng |
| Instituição de defesa: |
Universidade Federal de Goiás
|
| Programa de Pós-Graduação: |
Programa de Pós-graduação em Nanotecnologia Farmacêutica em Rede (FF)
|
| Departamento: |
Faculdade de Farmácia - FF (RMG)
|
| País: |
Brasil
|
| Palavras-chave em Português: |
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| Palavras-chave em Inglês: |
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| Área do conhecimento CNPq: |
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| Link de acesso: |
http://repositorio.bc.ufg.br/tede/handle/tede/13660
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Resumo: |
Introduction: Nanomedicines, including liposomes, have been studied and applied to improve clinical efficacy and safety of drugs. To tailor the pharmacokinetics of these systems, a hydrophilic polymer coating of poly(ethylene glycol) (PEG) has been used to prolong circulation time. It is believed that PEG prevents the interactions of liposomes with various clearance-enhancing proteins, therefore promoting their long circulation time. Vast literature supports that the complement cascade is responsible for the majority of the immune response against liposomes, including a rapid clearance. However, in a previous study, our group has shown, using transgenic animals unable to activate the complement cascade, that this pathway of the innate immunity could not explain the differences in early clearance observed with various non-liposomal drug delivery systems. Objectives: The purpose of this work is to explore the role of complement on the elimination of intravenously administered liposomes in rodents, and to study the impact of the size of liposomes in their behavior in serum. Methodology: Liposomes of 100 and 400 nm diameter were prepared and incubated in serum with and without EDTA in order to evaluate the effect of complement on the release of hydrophilic content. To explore the role of complement activation on the pharmacokinetics of liposomes, animals were treated intraperitoneally with cobra venom factor 24 and 12 h before the intravenous injection of radiolabeled liposomes. Radioactivity of blood samples was assessed by scintillation counting. Results and discussion: Complement proteins seem to trigger the release of the content from 400 nm non-PEGylated liposomes in rat serum, conversely, no effect was shown in smaller 100 nm non-PEGylated liposomes. As expected, the non-PEGylated liposomes showed faster elimination than PEGylated liposomes in rodents. At a lipid dose of around 20 mg.kg- 1, the abrogation of the complement cascade did not interfere in the circulation time of either PEGylated and non-PEGylated liposomes. However, at lower doses, the complement cascade seems to play a role on the faster elimination of non-PEGylated liposomes. Conclusion: The activation of the complement cascade may be not enough to predict the elimination time of PEGylated and non-PEGylated liposomes |
