Degradable Ureido‐Polycarbonate Block Copolymers with a Complex UCST Thermoresponse

In this work, amphiphilic block copolymers (BCs) consisting of a hydrophilic poly(ethylene glycol) methyl ether (PEG) and a degradable polycarbonate block derived from 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) with pendant ureido units, along with corresponding homopolycarbonates are described. Polymers are synthesized by combining ring opening polymerization (ROP) and thiol-ene/yne functionalization to incorporate UCST-promoting ureido groups. For homopolycarbonates, increasing the ureido groups density along the polymer chain facilitates the upper critical solution temperature (UCST)-type thermoresponse in water. Because of their amphiphilic character, BCs form stable self-assemblies either by direct dispersion in water, co-solvent method or microfluidics. Upon heating, these self-assemblies swell, and collapse due to extensive hydration of the polycarbonate block, rather than becoming solubilized. Thermoresponsiveness is analyzed in terms of the number of ureido groups in the polycarbonate for a given polycarbonate block length as well as the length of polycarbonate block. As a proof of concept, the potential of these self-assemblies as thermoresponsive drug nanocarriers is evaluated, using curcumin as a hydrophobic model drug.