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Micro et Nanomédecines translationnelles

Lipid nanocapsules hydrogel combined with the NFL-TBS.40-63 peptide to prevent glioblastoma recurrences

Lipid nanocapsules hydrogel combined with the NFL-TBS.40-63 peptide to prevent glioblastoma recurrences

Directeur de Thèse: Dr Guillaume Bastiat

Abstract :

Glioblastoma (GBM) is an aggressive malignant brain tumor. Despite the standard treatment: surgical resection and radio/chemotherapy, the survival median is low: from 15 to 18 months. Mainly due to its invasive nature,systematic recurrences appear after the current standard of care, causing the death of the patients. In this thesis, we evaluated the feasibility and efficacy of a hydrogel of lipid nanocapsules(LNCs) functionalized with the NFL-TBS.40-63 peptide (NFL) for local treatment of GBM.The hydrogels were prepared using a temperature phase inversion process. Two crosslinking agents (cytotoxic and non-cytotoxic) were used to allow the auto-association of the LNCs in a tridimensional network. After the evaluation of the limitations of the centrifugal filtration technique, the NFL peptide adsorption at the LNCsurface was quantified using an automatized size exclusion chromatography method. This adsorption is a kinetic process depending on the surface charge and the size of the LNCs,the surfactant composition of the LNC surface, and the NFL concentration. The presence of the peptide does not disturb the viscoelastic properties of the hydrogels and the original hydrogel structure allows a sustained release of the NFL-adsorbed NCLs. Despite the faster internalization of NFL-adsorbed LNCs in a couple of GBM cells in comparison to the NFL-free LNCs, the improved cytotoxicity seems to be dependent to the cell nature. These hydrogels could be injected directly into the GBM resection cavity, which will make them a promising tool fort he local treatment of GBM

Keywords : lipid nanocapsules, targeting peptide, hydrogel, glioblastoma

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