Detalhes bibliográficos
| Ano de defesa: |
2011 |
| Autor(a) principal: |
Gaeti, Marilisa Pedroso Nogueira
 |
| Orientador(a): |
Lima, Eliana Martins
|
| Banca de defesa: |
Lima, Eliana Martins,
Alonso, Antônio,
Amaral , André Correa,
Valadares, Marize Campos |
| Tipo de documento: |
Dissertação
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Federal de Goiás
|
| Programa de Pós-Graduação: |
Programa de Pós-graduação em Ciências da Saúde (FM)
|
| Departamento: |
Faculdade de Medicina - FM (RG)
|
| 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/4337
|
Resumo: |
Liposomes containing 4-nerolidylcatechol (4-NC), the main metabolite isolated from Pothomorphe umbellata, were obtained and characterized. The influence of liposomal encapsulation on the chemical stability of 4-NC and on the cytotoxicity profile of this drug was evaluated. Liposomal dispersion was prepared by lipid film hydration followed by extrusion through polycarbonate membranes. Entrapment efficiency for 4-NC was approximately 92%. Liposome mean diameter was 100 nm with a polydispersity index below 0.13. 4-NC encapsulated in liposomes (L4-NC) and in methanolic solution (F4-NC) were submitted to forced degradation tests (photostability and acid/base hydrolysis), monitored by HPLC. Photodegradation assay was performed according to ICH Guidelines, using a photostability chamber equipped with both UV and white light sources. Results demonstrated that liposomal encapsulation was able to markedly reduce 4-NC degradation rates for all the forced degradation conditions tested. L4-NC showed a half-live approximately 15% higher than F4-NC under light exposure. After 72 hours, acid and base hydrolysis of F4-NC lead to 13 and 16% of degradation, respectively. However, no degradation was observed in L4-NC. EPR spectra of the liposomal membrane showed that greatest changes in membrane properties were obtained when 5-doxyl stearic acid was used as the spin label, showing a marked decrease in the fluidity of the bilayer and indicating that 4-NC was located near the polar head groups of the phospholipid bilayer. F4-NC induces hemolysis under isotonic conditions whereas liposomal encapsulation protects erythrocytes from lysis. Following incubation with K562 cells, 4-NC showed a concentration-dependent cytotoxicity profile, while L4-NC exhibited a time and concentration-dependent profile, characterizing the liposomal formulation as a controlled release system. |
