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Theses

Franchissement de barrières biologiques, mécanisme d'action et devenir subcellulaire de nanovecteurs d'agents anticancéreux pour la thérapie des gliomes

Abstract : By focusing on drug administration within and to the central nervous system and notably on glioblastoma, the aim of the present PhD thesis work was to develop tools and evaluate the behavior of particulate nanocarriers as regards to biological barrier crossing. Three types of nanocarriers with sizes varying from 20 to 100 nm were evaluated: polysaccharide nanoparticles, PLGA nanoparticles, and lipid nanocapsules. The behavior of those objects concerning blood constituents allowed to define that coating with transferrine of PLGA nanoparticles or insertion of phospholipids or BSA within polysaccharide nanoparticles reduce their recognition by the reticulo-endothelial system and improve their plasma-resident time. Those surface modifications are also associated with a possibility of internalization in F98 glioma target cells essentially influenced by the lipid or polymeric nature or the carrier. Clear-cut evaluation of the cellular and subcellular behavior of LNC within F98 cells allowed to demonstrate that if the nature of the carrier is involved, notably considering the recruitment of cholesterol-dependant endocytic pathways, the size, correlated to amounts of surfactant provided, had also its significance. 20nm LNC are consequently the more apt to allow lysosome escape of transported drug and demonstrated higher pharmacological activities in inducing cell death through paclitaxel loading. Those results provide, therefore, original links between the subcellular behavior of nanocarrier and the bioavailability anticancer drugs. New potentialities of biological barrier crossing and size-dependent abilities were demonstrated. Those observations emphasize the interest of developing comparative studies in order to rationalize the use of a define nanocarrier for a given drug on a given target. Regarding new nanomedicines development, it demonstrates the importance to establish justification between biological behavior of nanocarriers and their therapeutic relevance.
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https://tel.archives-ouvertes.fr/tel-00482293
Contributor : Anne-Marie Plé <>
Submitted on : Monday, May 10, 2010 - 10:57:04 AM
Last modification on : Friday, October 23, 2020 - 4:36:38 PM
Long-term archiving on: : Thursday, September 16, 2010 - 2:15:12 PM

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  • HAL Id : tel-00482293, version 1

Citation

Archibald Paillard. Franchissement de barrières biologiques, mécanisme d'action et devenir subcellulaire de nanovecteurs d'agents anticancéreux pour la thérapie des gliomes. Neurosciences [q-bio.NC]. Université d'Angers, 2009. Français. ⟨tel-00482293⟩

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