Испитивање температурне осетљивости радијационо синтетисаних кополимерних хидрогелова олиго(пропилен-гликол)-метакрилат

Abstract

The doctoral dissertation, "Temperature Sensitivity Testing of Radiation-Synthesized Copolymer Hydrogels oligo(propylene-glycol)-methacrylate", arose from researchers' long-standing interest in discovering new biomaterials by testing a "smart" class of hydrogels that could meet their needs in biomedical applications. The aim of the study was to examine the temperature sensitivity of a new class of hydrogels and functionalized copolymers based on oligo(propylene glycol) methacrylate (OPGMA). All hydrogels were obtained by radical copolymerization of monomers or mixtures of monomers induced by high-energy gamma radiation in the presence of a crosslinker in the Radiation Unit for Industrial Sterilization of the Vinča Institute of Nuclear Sciences and can be classified into three series. The first series consists of copolymer hydrogels poly(oligo(propylene glycol) methacrylate) (POPGMA) functionalized by the addition of inert monomer, 2-hydroxyethyl methacrylate (HEMA), and small amounts of pH-sensitive, itaconic acid (IA), i.e., "smart" hydrogels with dual responsiveness, temperature, and pH of the medium. By varying the proportion of copolymer components, it was discovered that a copolymer hydrogel with a 4 wt% itaconic acid concentration exhibits a temperature transition in the range of physiological temperature values, implying that this hydrogel has the potential to be employed in biomedicine. The second series consists of methacrylate copolymer hydrogels with oligo(propylene glycol) (OPG) and oligo(ethylene glycol) (OEG) pendant chains, poly(propylene glycol6-ethylene glycol3) methacrylate (PPG6EG3MA) and poly(propylene glycol3-ethylene glycol6) methacrylate (PPG3EG6MA). Obtained results showed temperature sensitivity, as well as high values for cell viability and low hemolytic activity, i.e., the obtained hydrogels, meet in vitro biocompatibility and these hydrogels could be used in cancer treatment using magnetic and/or photothermal hyperthermic therapy. The third series of hydrogels consist of copolymer hydrogels with different proportions of oligo(propylene glycol) methacrylate (OPGMA) and oligo(ethylene glycol) methacrylate (OEGMA), P(OPGMA/OEGMA) hydrogels with initially different proportions of PG and EG units. Temperature sensitivity testing of this series of hydrogels revealed a linear relationship between the share of EG units and the temperature of the volume transition, and that hydrogels in pH 7.4 environmental conditions with a share of 42 mol% OEGMA monomers have the highest drug release potential. Characterization of hydrogels was performed using scanning electron microscopy (SEM), infrared spectroscopy with Fourier transform (ATR-FTIR), ultraviolet and visible spectroscopy (UVVis), differential scanning calorimetry (DSC), and by determining the degree of swelling in buffer solutions in a wide range of temperatures and pH values. Methods for testing the biocompatibility of hydrogels, cytotoxicity tests, and hemolytic activity tests were also used, and diclofenac sodium was used as a model drug for the analysis of controlled drug release in vitro. Synthesized hydrogels based on OPGMA have demonstrated good biocompatibility and the potential for use as carriers in controlled drug release systems in biomedicine.