Synthesis of thermosensitive copolymers of N-isopropylacrylamide with 2-aminoethylmethacrylate hydrochloride

Objectives. Due to the increasing number of oncological diseases, active research into developing new radiopharmaceuticals is underway. Thermosensitive copolymers have valuable physicochemical properties that can be harnessed to develop therapeutic radiopharmaceuticals for treating solid tumors. The aim of this study was to develop a method for producing thermosensitive copolymers that can find use as radionuclide carriers to create therapeutic radiopharmaceuticals for treating solid tumors.

Methods. Using radical copolymerization in polar solvents, we synthesized water-soluble copolymers based on N-isopropyl acrylamide and 2-aminoethyl methacrylate hydrochloride. The resulting copolymers were characterized in terms of molecular composition and hydrodynamic properties using gel permeation chromatography, IR spectroscopy, potentiometry, and viscometry. Changes in optical density during temperature scanning helped determine the phase transition temperature (PTT) of aqueous copolymer solutions.

Results. We developed a method for preparing copolymers of N-isopropylacrylamide with 2-aminoethyl methacrylate using radical copolymerization in water and isopropanol with a content of 2-aminoethyl methacrylate hydrochloride in a copolymer up to 23 mol %. We studied how the second comonomer affected the PTT of the aqueous copolymer solutions. An increase in the content of 2-aminoethyl methacrylate in the copolymer caused the PTT to increase. We found that the change in the PTT depending on the content of 2-aminoethyl methacrylate units in the copolymer had a straightforward relationship with its content up to 17 mol %. The use of physiological saline as a solvent led to a temperature decrease of the phase transition by two degrees.

Conclusions. The method of producing thermosensitive copolymers by radical copolymerization in isopropanol does not allow creating a radionuclide carrier. Solutions of the obtained lowmolecular weight oligomers form coacervate solutions, which will inevitably cause the radionuclide to spread throughout the body. The copolymers obtained by radical copolymerization in water with the content of the second comonomer 2-aminoethyl methacrylate from 10–17 mol % can be used as a radionuclides carrier provided that a physiological solution of sodium chloride is used as a solvent. 

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