Micellization of novel biocompatible thermo-sensitive graft copolymers based on poly(ε-caprolactone), poly(N-vinylcaprolactam) and poly(N-vinylpyrrolidone)

This study reports the metal-free synthesis, the characterization and the micellization of a novel type of amphiphilic biocompatible and thermo-sensitive graft copolymers. It comprises a hydrolytically degradable hydrophobic poly(epsilon-caprolactone) (PCL) backbone and water-soluble thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-based side chains. The synthesis of these PCL-g-PNVCL graft copolymers, with controlled graft density, was carried out in a three-step process: (i) preparation of a chloro-functionalized PCL backbone by metal-free ring-opening copolymerization of epsilon-caprolactone and alpha-chloro-epsilon-caprolactone, (ii) generation of a macro-RAFT initiator by nucleophilic substitution of the chioro groups with potassium ethyl xanthogenate, and (iii) free radical controlled RAFT-Madix polymerization of NVCL. In order to tune the LCST of these graft copolymers with the human body temperature, a RAFT copolymerization of NVCL with N-vinylpyrrolidone (NVP) was performed in another series of reactions. Such PCL-g-PNVCL copolymers with a constant graft density of 15 grafting sites, DPn,backbone = 120 and DPn,average (per graft) = 54 lead in aqueous medium to stable micelles having an average hydrodynamic diameter Dv of 38 nm. The spherical morphology of these micelles was observed by TEM. Their thermo-sensitivity was further confirmed and a LCST value of 32 degrees C was determined. The incorporation of 10 or 20 mol% NVP units in the grafts of the PCL-g-P(NVCL-co-NVP) copolymers leads to a shift of LCST to higher temperatures in the range of 38- 40 degrees C.