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APPLICATION DES NANOCAPSULES LIPIDIQUES CHARGEES EN FERROCIPHENOL DANS LE TRAITEMENT DU GLIOBLASTOME

Abstract : This thesis work aims at optimizing the chemotherapy of glioblastoma by lipid nanocapsules (LNC) loaded with an innovant organometallic anticancer drug, the ferrociphenol (FcdiOH). To this end, various routes of administration for drug delivery were investigated: convectionenhanced delivery (CED) (60μL LNC, 0.36mg of FcdiOH/rat), intra-carotid injection and intravenous injection (400μL LNC, 2.4mg of FcdiOH/rat). On 9L orthotopic model, antitumoural effect of FcdiOH exhibited a dose dependant effect. The local administration by CED of an iso-osmolar suspension of FcdiOH-LNC significantly increased the median survival time of treated rats as compared to untreated controls (28.5 days versus 25 days). The coating with longer chains of poly(ethylene glycol) (DSPE-mPEG2000) allowed improving the blood circulation time of such pegylated LNC with 4-fold longer half-life and 1.65-fold larger area under the curve than these of classic ones. This leaded to the eradication of subcutaneous tumour after a single intravenous injection of DSPE-mPEG2000-FcdiOH-LNC, showing the efficacy of passive targeting with these nanovectors. In addition, the intracarotid injection represents a promising route of administration for drug delivery to the brain. Interestingly, the intracarotid treatment with DSPE-mPEG2000-FcdiOH-LNC dramatically prolonged the survival time of intracranial 9L-tumour-bearing rats (median of 30 days). Finally, the incorporation of NFL-TBS peptide at the LNC surface seems to be an interesting approach through the active targeting, as preliminary studies evidenced one rat surviving until day 44.
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Submitted on : Friday, February 10, 2012 - 5:19:34 PM
Last modification on : Wednesday, October 20, 2021 - 3:19:05 AM
Long-term archiving on: : Friday, May 11, 2012 - 3:00:32 AM

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  • HAL Id : tel-00668962, version 1

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Ngoc Trinh Huynh. APPLICATION DES NANOCAPSULES LIPIDIQUES CHARGEES EN FERROCIPHENOL DANS LE TRAITEMENT DU GLIOBLASTOME. Sciences pharmaceutiques. Université d'Angers, 2011. Français. ⟨NNT : ⟩. ⟨tel-00668962⟩

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