with five different pH-sensitive linkers (Figure , monomers A to E), followed by their RAFT copolymerization at 10 wt % with HPMA to give a small library of P(HPMA-co-M-Dxm) (with M = A to E) water-soluble polymer prodrugs. Under acidic conditions (pH 5 and 6), P(HPMAco-E-Dxm) gave the fastest Dxm release and P(HPMA-co-D-Dxm) the slowest, while they were all relatively stable (< 10 % release after 500 h) under physiological conditions (pH 7.4). In It is interesting to note that increasing the Dxm content from 10 to 24 wt % led to the appearance of a phase transition temperature and the formation of a hydrogel around 30 °C. Molecular dynamics simulations revealed a correlation between Dxm content and drug release kinetics from the hydrogel, as the higher the Dxm content, the slower the release, which was probably due to two factors: (i) an increase in hydrophobic aggregation for higher drug amounts and (ii) a more limited exposure (on the surface of the hydrogel only) to the releasing medium.