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.

Intelligent copolymers based on poly (N-isopropylacrylamide) PNIPAm with potential use in biomedical applications. Part i: PNIPAm functionalization with 3-butenoic acid and piperazine

The synthesis and characterization of the thermosensitive copolymers based on Poly (N-Isopropylacrylamide) (PNIPAm) and 3-butenoic acid and functionalized with piperazine was carried out. The free radical polymerization of the PNIPA copolymer with 3-butenoic acid was performed under microwave radiation. After obtaining this copolymer, the carboxyl groups present in the copolymer chain were activated with 1-ethyl- (3-3-dimethylaminopropyl) carbodiimide in the presence of N-hydroxysuccinimide, improving its reactivity to incorporate the piperazine through its amino group. The characterization consisted: differential scanning calorimetric and ultraviolet-visible spectrophotometry to determine the LCST phase transition temperature, ranging from (30-35)°C. Structurally it was analyzed by infrared spectroscopy. A morphological analysis was performed using scanning electron microscopy, after simulating an injectable process, with the objective to observe internally the porosity and interconnectivity. The biocompatibility was evaluated through hemocompatibility tests and it was observed that the copolymers obtained were not cytotoxic. In base of the results, the chemical structure of these new copolymers confers a functionality that allows them to serve as nuclei to graft other molecules, such as polysaccharides. Then, the results obtained on the LCST temperature, porosity, interconnected pore network morphology, the ability to be injectable and the biocompatible nature of these copolymers are indicative that these new synthetic biomaterials have the potential to be used in biomedical, pharmacological and for tissue engineering. Also, once their biocompatibility was demonstrate, they may serve to generate interesting compounds having chemical anchor points for the possible addition of polysaccharides using insertion reactions, thereby generating graft copolymers with potential use in biomedical applications.

Removal of metal ions from aqueous effluents involving new thermosensitive polymeric sorbent

In this work, new thermosensitive copolymers bearing phosphonated groups were synthesized and used to remove metal pollution. Sorption properties are brought by hydrolyzed (dimethoxyphosphoryl)methyl 2-methylacrylate (hMAPC1) monomer. N-n-propylacrylamide (NnPAAm) led to the thermoresponsive properties of the copolymers. Low lower critical solution temperature (LCST) values were observed, ranging between 20 and 25 °C depending on the molar ratio of each monomer in the copolymer. Sorption properties of these copolymers towards nickel ions were evaluated for increasing temperatures (10–40 °C), Ni ion concentrations of 20 mg L−1 and pH values between 3 and 7. Best results were observed for temperatures just lower than the LCST (20 °C), when the copolymer was fully soluble in water solution. For temperature higher than the LCST, phosphonic diacid groups accessibility was considerably reduced by the precipitation of the thermosensitive part of the copolymer leading to lower sorption properties. In these conditions, the highest Ni removal by the copolymer was observed for pH = 7, when there was almost no competition between the sorption of H+ and Ni2+ ions on the phosphonic acid groups. These optimal conditions enabled removal of about 70% of the nickel in the synthetic effluent.