New Binary Thermoresponsive Polymeric System for Local Chemoradiotherapy

Radiolabeled thermoresponsive polymers (TRPs) with cloud-point temperatures between room temperature and body temperature may have an advantage for local radiotherapeutical applications because TRPs may be isotopically labeled in solution. at room temperature and injected as a solution, and at the site of application, the polymers form a depo because of phase separation at body temperature. A new polymeric drug-delivery system designed for combined local chemoradiotherapy with an injectable TRP bearing a radionuclide and the hydrophobic moiety doxorubicin (DOX) was synthesized and characterized. In the system, DOX served as an antiproliferative agent with known synergic effects with ionizing radiation and the hydrophobic moiety controlling bioerosion and elimination of the system at the same time. DOX was bound to the polymer carrier by a hydrolytically labile N-glycosylamine bond. Hydrolysis of the N-glycosylamine bond thus controlled the DOX release and dissolution of the system in the model aqueous milieu. DOX was slowly released during incubation in aqueous milieu at 37 degrees C, which caused complete dissolution of the bioerodable polymer within about 2 weeks. The model radionuclide iodine 125, bound to a small amount of poly(N-isopropylacrylamide-co-N-methacryloyl tyrosinamide), was retained in the separated phase and also slowly dissolved during the incubation. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 111: 2220-2228, 2009