Pegylated thermally responsive block copolymer micelles and nanogels via in situ RAFT aqueous dispersion polymerization

A very straightforward approach was developed to synthesize pegylated thermoresponsive core-shell nanoparticles in a minimum of steps, directly in water. It is based on RAFT-controlled radical crosslinking copolymerization of N,N-diethylacrylamide (DEAAm) and N,N-methylene bisacrylamide (MBA) in aqueous dispersion polymerization. Because DEAAm is water-soluble and poly(N,N-diethylacrylamide) (PDEAAm) exhibits a lower critical solution temperature at 32 °C, the initial medium was homogeneous, whereas the polymer formed a separate phase at the reaction temperature. The first macroRAFT agent was a surface-active trithiocarbonate based on a hydrophilic poly(ethylene oxide) block and a hydrophobic dodecyl chain. It was further extented with N,N-dimethylacrylamide (DMAAm) to target macroRAFT agents with increasing chain length. All macroRAFT agents provided excellent control over the aqueous dispersion homopolymerization of DEAAm. When they were used in the radical crosslinking copolymerization of DEAAm and MBA, the stability and size of the resulting gel particles were found to depend strongly on the chain length of the macroRAFT agent, on the concentrations of both the monomer and the crosslinker, and on the process (one step or two steps). The best-suited experimental conditions to reach thermosensitive hydrogels with nanometric size and well-defined surface properties were determined.