Synthesis and thermoresponsive behavior of double hydrophilic graft copolymer based on poly(2-methyl-2-oxazoline) and poly (2-ethyl-2-oxazoline)

A recent challenge in polymer self-assembly is the utilization of double hydrophilic graft copolymers (DHGC) in view of biomedical applications. Here we describe, for the first time, a platform of biocompatible DHGC fully based on poly(2-alkyl-2-oxazoline) leading to stimuli-responsive self-assemblies. This original DHGC platform was composed of backbone poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)) and poly(2-ethyl-2-oxazoline) (PEtOx) grafts. A "grafting onto" approach based on the combination of cationic ring-opening polymerization (CROP) technique and "click chemistry" CuAAc reaction, was successfully used to synthesize poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline)-g-poly(2-ethyl-2-oxazoline) (P(MeOx-co-PentOx)-g-PEtOx) copolymer conjugates of varying backbone and side chain lengths. These purely hydrophilic copolymers demonstrated self-assembling behavior in aqueous solution, showing a characteristic double hydrophilic behavior originating from building blocks immiscibilities. Self-associated structures with spherical morphologies have been evidenced by DLS and cryo-TEM. The sizes and the efficiency of self-association were mainly controlled by the concentration of the graft copolymer and by the molar ratio of the different hydrophilic compounds. In addition, thermoresponsive properties of these copolymers were studied by turbidimetry and DLS. From purely hydrophilic at low temperature, the copolymers showed amphiphilic characters at temperatures close to the cloud points (CP). Interestingly, cloud points were not controlled by the PEtOx graft length as it has been reported for PEtOx homopolymers but it depended mainly upon the PEtOx content of the copolymer, with a critical value around 75 PEtOx wt%. Addition of a kosmotropic salt (Na2SO4) allowed to trigger CPs from 80. C till 26.C. The self-assembling properties of this family of hydrophilic and biocompatible copolymers may offer promising prospect in the field of biomedical applications as bioreactors.