The effect of mPEGA/EHA ratio and copolymer composition on the solution behavior of amphiphilic, comb‐shape copolymers synthesized via Cu(0)‐mediated SET‐LRP for potential drug delivery applications

Abstract

Comb-shape, block copolymers from hydrophilic poly(ethylenglycol) monomethyl ether acrylate (mPEGA, A) and hydrophobic 2-ethylhexyl acrylate (EHA, B) are synthesized by copper(0)-mediated single-electron transfer living radical polymerization (SET-LRP) via sequential addition of the two monomers, resulting in different compositions (AB, ABA, BAB, BA), molar masses, and mPEGA/EHA ratios. All polymers show narrow molar mass distributions and molecular weights of 7.7-25.50 kg mol-1, demonstrating precise control over the polymerization and molecular weights through the utilization of SET-LRP. Kinetic experiments are conducted to investigate the polymerization behavior of mPEGA and EHA in N,N-dimethylformamide as a rather uncommon solvent for SET-LRP further underlining a living-type polymerization. Amphiphilic properties are investigated by critical micelle concentration (CMC) measurements and formation of micelles in water. A reverse relation between mPEGA/EHA ratio and CMC values reveals that an increased hydrophobicity leads to decreased CMC values. The self-assembly behavior of polymers in water confirms the formation of uniform and stable micelles in water with a size between 12 and 184 nm depending on the composition of the polymers. With increased hydrophilicity, micelle sizes increase as well. In vitro tests of the obtained polymers show excellent biocompatibility even at high concentrations further affirming their suitability for drug delivery applications.