Tailor-made degradable copolymers for the design of advanced drug delivery systems

Over the last decades, polymer micelles have attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems.
The goal of this thesis was centered on the design of new smart nanocarriers and more particularly on the basis of reversibly redox-cross-linked polymer micelles. The first part of that work was dedicated to the synthesis of new macromolecular architectures associating biodegradable hydrophobic polymers such as polyester (e.g. PCL), polycarbonate (e.g. PTMC) or also polyphosphate (e.g. PBODOP) and the water soluble poly(ethylene oxide) (PEO) frequently used due to its biocompatible properties. Well-defined block copolymers have been synthesized by ring-opening polymerization.
The second part of that work focused on the cross-linking of the hydrophobic block in order to obtain well stabilized micelles. The copolymerization of α-chloro-ε-caprolactone (αClεCL) allows to easy functionalize the hydrophobic block in order to reversibly cross-link the future micelle core by the addition of a disulfide bearing cross-linker. The self assembly of theses copolymers and redox-dependent micellization behaviours have been studied by diffusion light scattering and transmission electronic microscopy.
Finally, the potential of these redox-sensitive micelles as active drug delivery system has been analysed by investigating their stealthy behaviours using the complement activation (CH50) test, their cytotoxicity, their cellular internalization and also the redox-sensitive profile of a hydrophobic dye.