self-assembly in solution; micelle; stimuli responsive micelle
Abstract :
[en] Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(E-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment.
Research Center/Unit :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Chemistry Materials science & engineering
Author, co-author :
Van Butsele, Kathy; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Morille, M.; LUNAM Université et INSERM, Angers, France > Ingénierie de la Vectorisation Particulaire
Passirani, Catherine; LUNAM Université et INSERM, Angers, France > Ingénierie de la Vectorisation Particulaire
Legras, P.; University of Angers, France > Service Commun Animalerie Hospito-Universitaire
Benoit, J.-P.; LUNAM Université et INSERM, Angers, France > Ingénierie de la Vectorisation Particulaire
Varshney, S. K.; Polymer Source, Montreal, Canada
Jérôme, Robert ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Jérôme, Christine ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Language :
English
Title :
Stealth properties of poly(ethylene oxide)-based triblock copolymer micelles: A prerequisite for a pH-triggered targeting system
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture
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