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Doctoral Thesis
DOI
10.11606/T.5.2007.tde-12062007-100409
Document
Author
Full name
Giovani Marino Favero
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Bydlowski, Sergio Paulo (President)
Abdallah, Kald Ali
Barros, Myrthes Anna Maragna Toledo
Pesquero, João Bosco
Zyngier, Szulim Ber
Title in Portuguese
Nanoemulsão contendo 7-cetocolesterol (LDE/7KC) promove inibição do crescimento de melanoma em camundongos e aumento de sobrevida
Keywords in Portuguese
Cetocolesteróis
Emulsões
Farmacocinética
Lipoproteínas do colesterol LDL
Melanoma experimental
Receptores LDL
Abstract in Portuguese
7-cetocoleterol (7KC) é um oxisterol conhecido por inibir a proliferação celular e por ser citotóxico. Desenvolvemos uma nanoemulsão contendo 7KC (LDE/7KC) que demonstrou efeito anti-proliferativo sobre as linhagens RPMI 8226 (mieloma) e melanoma (B16F10), in vitro, sendo preferencialmente captada via receptores de LDL. No presente trabalho avaliamos, in vivo, a cinética plasmática, biodistribuição, ação anti-tumoral e parâmetros tóxico-hematológicos em camundongos portadores de melanoma. A cinética plasmática apresentou um decaimento estatisticamente igual entre os animais portadores de melanoma e não portadores. Em relação à biodistribuição da nanoemulsão, houve um acúmulo de seus componentes radioativamente marcados, principalmente no fígado e no tumor, sugerindo sua captação via receptores de LDL. LDE/7KC promoveu uma redução superior a cinqüenta por cento do tamanho do tumor, que apresentou maior área de necrose e menor quantidade de vasos. Nos camundongos tratados com LDE/7KC houve um aumento da sobrevida. As análises toxico-hematológicas demonstraram que a nanoemulsão apresentou pouca ou nenhuma toxicidade. Os resultados demonstram a possibilidade da utilização da nanoemulsão LDE/7KC como um agente no tratamento do câncer, com poucos efeitos colaterais, devido a sua seletividade aos receptores da LDL.
Title in English
A 7-ketocholesterol containing-nanoemulsion (LDE/7KC) inhibits growth of melanoma tumor in mice and increases survival rate
Keywords in English
Emulsions
Ketocholesterol
LDL lipoprotein
LDL receptor
Melanoma
Pharmacokinetics.
Abstract in English
7-ketocholesterol (7KC) is an oxysterol known to inhibit cell proliferation and to be cytotoxic. A nanoemulsion containing-7KC (LDE/7KC) was shown to have antiproliferative effects on RPMI 8226 myeloma cell line and melanoma (B16F10), in vitro. This particle is taken up mainly by LDL receptors. Here we have evaluated the plasma kinetic, biodistribution, anti-tumoral action and hematologic toxicity of LDE/7KC in melanoma bearing mice. The nanoemulsion accumulated in the liver and tumor, tissues with a high expression of LDL receptors. LDE/7KC promoted a tumor size reduction over fifty percent. An increased necrosis area and a decreased amount of blood vessels were found. An increased survival rate was observed. The hematolgic analyses demonstrated a lack of toxicicity. The results shows the possibility to use the LDE/7KC nanoemulsion as an agent for cancer treatment, with few collateral effects probably due to its internalization by LDL receptors.
 
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GiovaniMarinoFavero.pdf (670.62 Kbytes)
Publishing Date
2007-07-02
 
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