Synthesis of amphiphilic graf copolymers by combination of synthetic and bio-derived polymers for obtaining nanoparticles and nanofibers for biomedical and industrial applications

Abstract

The development of new polymer materials from renewable sources that are less aggressive to the environment has received much attention in recent years, especially polymers that have specific applications based on properties like biodegradability, biocompatibility and stimuli-responsiveness. For this reason, melanin-free pullulan is an alternative for the synthesis of polymers derived from petro-sources to produce amphiphilic graft-copolymers with a wide range of properties for biomedical and industrial applications. Thus, the aim of this project is to develop different types of amphiphilic graft-copolymers constituted of pullulan-g-poly(3-hydroxybutyrate-co-3-hydroxyvalerate), pullulan-g-poly(µ-caprolactone) and pullulan-g-poly(N-vinylcaprolactam) by the use of different synthetic strategies: reversible addition fragmentation chain transfer polymerization (RAFT/MADIX) of N-vinylcaprolactam starting by pullulan macro-RAFT agent, ring-opening polymerization (ROP) of the µ-caprolactone, transesterification of PHBHV and conjugation via 1,3-dipolar cycloaddition reaction between azides and alkynes (click chemistry). All polymers will be used for the production of self-assembled nanoparticles for controlled delivery systems. Aqueous solutions of the synthesized amphiphilic graft-copolymer in the presence of hydrophobic active substances (Ketoprofen) will be used to prepare nanoparticles using two methods: nanoprecipitation and emulsion-diffusion/solvent evaporation. Nanofibers with active substances will also be produced by electrospinning technique in partnership with Prof. Dr. Nicole Raymonde Demarquette at École de Technologie Supérieure in Montreal. Furthermore, two crosslinking agents will be tested in the reticulation of the pullulan-g-polymer in order to preserve the self-assembled structures and extend the applicability of these graft-copolymers in ink 3D-bioprint processes. (AU)