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Micro et Nanomédecines translationnelles

Polyphosphoesters for the design of organic and inorganic drug delivery systems

Directeur de Thèse : Pr Frank Boury

Résumé :

Polymers with repeating phosphoester linkages in the backbone are biodegradable and emerged as a promising class of novel biomaterials, especially in the field of drug delivery systems. The pentavalency of the phosphorus atom offers a large diversity of structures and as a consequence a wide range of properties for these materials. The thesis focused on the synthesis of novel well-defined diblock copolymers made of one hydrophilic polyethylene oxide (PEO) block and one polyphosphotriester (PPE) block bearing unsaturations as side-group, as a platform for the design of advanced drug delivery systems. Firstly, novel alkenyl PEO-b-PPE amphiphilic copolymers were self-assembled in water, taking profit of the unsaturations to prepare core cross-linked micelles. Doxorubicin could be successfully loaded by impregnation in these micellar nanocarriers leading to improved stability and loading as compared to the corresponding non-cross-linked systems.Besides, the alkynyl and allyl unsaturations of PEO-b-PPE copolymers were used to prepare novel double hydrophilic block copolymers exhibiting calcium complexation capabilities. They were found quite efficient as template for the formation of calcium carbonate particles providing particles of unprecedented small size, and high size homogeneity. The use of a supercritical carbon dioxide process with carboxylic acid containing copolymers allows reaching CaCO3 particles about 1.5 μm. Finally, we demonstrate that adding lysozyme to the process allows encapsulation of this enzyme into the CaCO3 carriers, the protein activity being better preserved by using the PPE-b-PEO as compared to more conventional hyaluronic acis as a template.