Synthesis, characterization and drug delivery applications of photoresponsive coumarin functional amphiphilick copolymers

Drug delivery systems are constantly evolving due to the need to minimize the side effects while increasing therapeutic activity. One of the most interesting drug delivery systems in recent times has been the self-assembly of stimuli-responsive amphiphilic block copolymers in aqueous solutions. Among them, the light-sensitive ones are of particular interest. These structures, which are capable of photo-reversible dimerization and are widely used in polymeric systems, generally proceed with a [4π + 4π] - or [2π + 2π] - cyclochemical mechanism which can be reversed by the application of light of a suitable wavelength. Progress in the synthesis of controlled-radical polymerisation (CRP) techniques and sensitive polymer synthesis through the development of "click" reactions has given tremendous opportunities in terms of flexibility, diversity and functionality in the design of polymeric building blocks. This versatility allows the nanostructures that the polymeric building blocks come together to form at the desired size and shape. The superiority of the CRP techniques over other simple techniques used in the synthesis of hydrophobic and hydrophilic copolymers makes it possible to control the molecular weight, sequence and end group functionality of the polymers. In this work, an amphiphilic block copolymers containing light dimerizable coumarin groups is synthesized using the advantage of controlled polymerization techniques and click reactions. Glycidyl methacrylate (GMA) monomer was polymerized by reversible addition-fragmentation chain transfer polymerization (RAFT) to form hydrophobic block, followed by azide functionalization of glycidyl units with NaN3 to attach a certain amount of coumarin groups via click reaction. Obtained polymer was used as macroinitiator in the RAFT polymerization of PEG methacrylate monomer and an amphiphilic copolymer was achieved. Polymers synthesized during this study were characterized by FT-IR, 1H NMR, UV, fluorescence ve DSC. At the last stage, dialysis method was used for micelle formation and doxorubicin (DOX) was loaded to micelles in order to examine drug loading efficiency of the micelles. Particle sizes of drug loaded and empty micelles were measured by DLS and compared with TEM images. Micelles were further irradiated at 350 nm wavelength in order to observe the alterations.