New bioerodable thermoresponsive polymers for possible radiotherapeutic applications

A new thermoresponsive system designed for local radiotherapy has been developed. In this system a radionuclide complex is entrapped in a thermoresponsive polymer locally precipitated at body temperature after injection of a polymer-complex solution into the tissue where a therapeutic effect is required. The lifetime of the system is controlled by the rate of polymer hydrolysis, its dissolution and elimination from the body. The thermoresponsive polymer with the cloud temperature (CT) below body temperature is based on copolymers of N-isopropylmethacrylamide with a methacrylamide-type comonomer containing hydrophobic n-alkyls of three different sizes (C(3), C(6) and C(12)) bonded by a hydrolytically labile hydrazone bond. Hydrolysis of hydrazone bond results in a copolymer soluble at body temperature. The copolymer containing 27.5 mole% of the comonomer with the C(6) moiety, which was chosen for further study, has the CT 22 degrees C and its phase separation is complete at 34 degrees C. Polymer dissolution is complete within 48 h at both pH 5.0 or 7.4. The model therapeutic radionuclide, (64)Cu, in the form of its hydrophobic chelate bis(quinolin-8-olato-N,O) [(64)Cu]copper, is efficiently kept hydrophobically entrapped in the phase-separated polymer until the dissolution by hydrolytic degradation is completed.