Main-chain degradable star polymers comprised of pH-responsive hyperbranched cores and thermoresponsive polyethylene glycol-based coronas

Core–shell polymeric architectures possessing stimuliresponsive behavior have great potential in triggered release systems, especially biomedical applications. Simultaneously achieving stimuliresponsive behavior and main-chain degradability is an interesting challenge facing modern polymer scientists. We report, the synthesis of star hyperbranched polymers possessing covalently cross-linked pH-responsive cores and linear thermoresponsive PEG-based coronas. Main-chain degradability throughout these structures is achieved via radical ring-opening polymerization of the cyclic ketene acetal 2-methylene-1,3-dioxepane, in combination with reversible-deactivation radical polymerization (RDRP) of methacrylate-based monomers. A two-step reversible addition–fragmentation chain-transfer (RAFT) polymerization is employed, initially facilitating the copolymerization of 2-(diethylamino)ethyl methacrylate and the divinyl cross-linker di(ethylene glycol) dimethacrylate to prepare pH-responsive hyperbranched polymers. Subsequent chain-extension with oligoethylene glycol methacrylate introduces a linear corona. Their ability to uptake and release hydrophobic actives in response to changes in pH is compared to a linear diblock copolymer micellar analogue. The star hyperbranched polymers have been modified post-polymerization by aminolysis to introduce reactive thiol sites, followed by thiol–maleimide click chemistry providing additional peripheral functionality. Hydrogels have also be prepared via disulfide bond formation between multiple star hyperbranched polymers. Finally, the synthetic methodology presented is further improved incorporating main-chain polyesters into both the hyperbranched core and linear corona. We describe the experimental conditions required to successfully prepare diblock and star hyperbranched polymers incorporating 2-methylene-1,3-dioxepane within each block via RAFT polymerization. The schizophrenic pH- and thermoresponsive self-assembly of these materials is investigated and their hydrolytic degradation presented.