Reference : Cross-linked pH sensitive polymer micelles for drug delivery systems
Scientific congresses and symposiums : Poster
Physical, chemical, mathematical & earth Sciences : Chemistry
Engineering, computing & technology : Materials science & engineering
http://hdl.handle.net/2268/8697
Cross-linked pH sensitive polymer micelles for drug delivery systems
English
Cajot, Sébastien [University of Liège (ULg) > Department of Chemistry > Center for Education and Research on Macromolecules (CERM) > >]
Jérôme, Christine mailto [University of Liège (ULg) > Department of Chemistry > Center for Education and Research on Macromolecules (CERM) > >]
8-Dec-2009
No
No
International
23èmes journées scientifiques du Groupe Thématique de Recherche sur la Vectorisation (GTRV)
7/12/2009 - 9/12/2009
B. Lebleu
N. Mignet
C. Passirani
M.-P. Rols
Paris
France
[en] biomaterial ; nanomedicine
[en] Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter.

In principle, the micelles core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(ɛ-caprolactone) (PCL), which serves as a reservoir for the incorporation of various lipophilic drugs. Water soluble poly(ethylene oxide) (PEO) is most frequently used to build the micelle corona because it is very efficient in preventing protein adsorption at surfaces and in stabilizing the micelles in the blood compartment, giving rise to particles invisible to the body defence system (so-called stealthy or long circulating particles). The tumour targeting of a cytotoxic agent refers to the passive accumulation of polymer nanocarriers to solid tumours (EPR effect) followed by active internalization in tumor cells. The internalization of the drug is required for cell death because most cytotoxic drugs act intracellularly. Accordingly, polymer micelles are usually modified by specific ligands. No-specific ligands can be used if their exposition is modulated by the pH decrease typical of tumour tissues. The release of the drug is ruled by diffusion and degradation of the biodegradable polymer used as reservoir. Even if micelles get a high stability in aqueous media thanks to their low critical micellar concentration, the dissociation of micelles is not always preserved when they are injected in the blood compartment. The cross-linking of the core of micelles by disulfide bridges will provide the stability of micelles after the administration and will release the drugs intracellularly by enzymatic breaking of disulfide bridges.

This work consists in the development of new macromolecular architectures for the targeting of tumour cells. pH sensitive copolymers able to micellize so as non-specific ligand like biotin is exposed on their surface in response to pH decrease typical for tumour tissues will be synthesized by the incorporation of pH-sensitive linkers, e.g. imine benzoïc linkers. In addition, the core of these new micelles will be cross-linked by disulfide bridges to prevent dissociation around healthy cells and trigger the drug release inside tumour cells.
Center for Education and Research on Macromolecules (CERM)
Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA
Researchers
http://hdl.handle.net/2268/8697
This poster was presented by Sébastien Cajot

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