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Apport des nanocapsules lipidiques dans le traitement local des gliomes malins: application à l'encapsulation de complexes lipophiles métalliques

Abstract : The aim of this work is the use of lipid nanocapsules (LNC) infused by convection-enhanced delivery (CED) for the local delivery of brain tumors. For therapeutic applications, LNC were loaded with two lipophilic metal-based complexes. The first one is a lipophilic complex of Rhenium 188 (188Re-SSS) which is investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant glioma. The second one is an anticancer drug with a ferrocene grafted on a tamoxifen skeleton and called ferrociphenol (Fc-diOH). When administered in LNC, 188Re tissue retention was greatly prolonged, and could eradicate tumors for an optimal dose of 8Gy as 33% of the animals were long-term survivors. The dose of 8 Gy proved to be a very effective dose, between toxic (10-12 Gy) and ineffective (3-4 Gy) ones. Fc-diOH-LNC showed many advantages such as a high drug loading capacity, and were able to be up-taken by glioma cells. Fc-diOH cytostatic activity was conserved after its encapsulation in LNC and was very effective on 9L-glioma cells as the IC50 was about 0.6μM. Interestingly, Fc-diOH-loaded LNC showed low toxicity levels when in contact with astrocytes which are slowly or non divided brain cells. Fc-diOH LNC treatment was able to lower significantly both tumour mass and volume evolution after 9L-cell implantation. Moreoever, the relationship between Fc-diOH-LNC and X-irradiations was synergistic. Combining an external irradiation of 18Gy (3x6 Gy) with CED of Fc-diOH-LNC increased the median survival time from 48% compared to the control group and 17% of the animals were long-terms survivors.
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Submitted on : Monday, February 1, 2010 - 11:38:31 AM
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  • HAL Id : tel-00451985, version 1

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Emilie Allard. Apport des nanocapsules lipidiques dans le traitement local des gliomes malins: application à l'encapsulation de complexes lipophiles métalliques. Médicaments. Université d'Angers, 2008. Français. ⟨tel-00451985⟩

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