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Synthèse et formulation des nanoparticules polymère ciblant l'E-sélectine : évaluation in vitro dans un modèle d'endothélium activé

Abstract : The objective of this work was to develop a delivery system targeting pathologically activated endothelium within inflamed, infectious, and some tumoral tissues. This system is composed of nanoparticles bearing sugar residues that are able to recognize and interact with E-selectin, a receptor expressed on the activated endothelial cells.We synthesized an amphiphilic block copolymer with the hydrophilic part terminated by a carbohydrate ligand. The construction was achieved by a combination of click chemisty, ring-opening polymerization and atom transfer radical polymerization. This copolymer was used to prepare nanoparticles of the core/shell type where the central hydrophobic body is surrounded with the hydrophilic shell that can stabilize the particles in aqueous media and limit their opsonisation. Active targeting was achieved by coupling an analogue of sialyl Lewis X, the physiological ligand of E-selectin to the end of the hydrophilic polymer chains on the surface of the particles.We were able to demonstrate in vitro the efficient association of these nanoparticles with defined surface properties with activated endothelial cells. This allowed us to validate our concept of active molecular targeting using this couple receptor/ligand couple. Such a system could be used to improve the therapeutically index and the biodistribution of anti-inflammatory and anti-tumor drugs.
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https://tel.archives-ouvertes.fr/tel-00747304
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Submitted on : Wednesday, October 31, 2012 - 1:04:10 AM
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  • HAL Id : tel-00747304, version 1

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Emile Jubeli. Synthèse et formulation des nanoparticules polymère ciblant l'E-sélectine : évaluation in vitro dans un modèle d'endothélium activé. Sciences agricoles. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : 2011PA114808⟩. ⟨tel-00747304⟩

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