Synthesis with RAFT method and characterization of drug and DNA carrier amphiphilic block copolymers

Block copolymers are an important class of polymer therapeutics because of their structural stability, low toxicity, high loading capacity, compact size, and solubility in water. Block copolymers form micelles in aqueous solutions with hydrophobic interactions if they are comprised of hydrophobic and hydrophilic blocks or, with electrostatic interactions if they are comprised of ionic and nonionic blocks or, with covalent bonds if they have suitable groups. Reduced interaction with physiological barriers and increased transport rates to target tissue are achieved by loading molecules such as DNA or drug into the core of these block copolymer micelles. In the study, amphiphilic block copolymers with the potential of DNA or drug delivery and release were synthesized by RAFT (reversible addition-fragmentation chain transfer) polymerization and characterized. Near monodisperse amphiphilic diblock copolymers, suitable for DNA or drug delivery and having functional groups for further modifications, were obtained using 4-vinylpyridine and oligoethyleneglycol methyl ether methacrylate (OEGMA) monomers. Functional groups in the structure of the polymer make it possible to bind targeting or marker molecules. Within the scope of this thesis, suitable RAFT agent and reaction conditions were determined for RAFT polymerization of 4-VP and OEGMA monomers. Then, OEGMA was polymerized with RAFT method and turned into macroCTA. Poly(OEGMA)-b-poly(4-VP) copolymer, which can be used in carrying hydrophobic drug, was obtained by polymerization of 4-VP monomer through the chain end of macroCTA. Subsequently, positively charged block copolymers, suitable for transport of DNA, were obtained by quaternization of 4-VP units in poly(OEGMA)-b-poly(4-VP). The all synthesized polymers were characterized by GPC, FTIR spectroscopy and NMR spectroscopy. Solution behavior of copolymers and complexes formed between quaternized copolymers and oligonucleotide inhibiting the c-myc gene were analyzed with light scattering spectroscopy, fluorescence spectroscopy, atomic force spectroscopy and UV spectroscopy. It was determend that poly(OEGMA)-b-poly(4-VP) block copolymers were individual chains in solution at pH values below 5 but they form micelles at pH values above 5. In addition, certain block copolymers were found to be temperature-sensitive. It was also observed that positively charged quaternized copolymers formed complexes with ODN and structure of formed complexes changed according to the temperature. In conclusion, temperature- and pH-sensitive amphiphilic block copolymers that can be used as drug carrier and temperature-sensitive positively charged block copolymers that can be used in gene therapy studies were obtained.