Design and synthesis of stimuli responsive polymeric nanostructures for drug delivery applications

Official URL: https://risc01.sabanciuniv.edu/record=b2586057_(Table of contents)

In recent years, advances in nanotechnology have pioneered new fields of research in biomedical applications. Nanostructures in different sizes, shapes, and surface charges have provided various advantages in controlled and targeted drug delivery systems with enhanced therapeutic efficiency. Moreover, nanostructures made from stimuli responsive materials provide more control on drug release kinetics as the stimuli they respond to, i.e temperature, pH, or concentration of a biomolecule, are commonly altered in targeted areas. This thesis focuses on design and synthesis of stimuli-responsive polymeric nanostructures for drug delivery applications. In the scope of this thesis, different nanostructures having stimuliresponsive properties were prepared via different synthesis techniques. Chitosan/poly (acrylic acid)/poly (N-vinyl caprolactam) core-shell nanoparticles (<100nm) were synthesized via surfactant-free batch emulsion polymerization, for pH&Temperature responsive controlled release of rose bengal. Niosome-ChitosangPNVCL composite nanoparticles (~80nm) were prepared via thin-film hydration method and polymeric coating for encapsulation of both a hydrophilic drug, rose bengal, and a hydrophobic drug, curcumin. Here, pH and temperatureresponsive drug release of these two therapeutic agents were enabled by the grafted polymer. Self-assembly albumin nanoparticles(<100nm) were synthesized via reducing agent-assisted desolvation method and glutathione responsive curcumin release was achieved thanks to the presence of intermolecular disulfide bonds at the structure. Finally, nanoparticles associated with electrospun drug delivery patches were prepared using rose bengal loaded chitosan nanoparticles(~50nm) synthesized via ionic gelation method and curcumin loaded poly(εcaprolactone) PCL nanofibers(<200nm) via electrospinning technique. Deposition of the nanoparticles onto the nanofibers was achieved via spray drying technique using a commercial airbrush. This study can pave the way for a facile fabrication route for dual drug-loaded implantable drug delivery patches and combining the advantages of nanoparticles and nanofibers in a single structure. All nanostructures fabricated have homogenous size dispersions and great encapsulation efficiencies (<80%). Drug loading and release studies about all these nanostructures were followed by using UV-Vis spectroscopy. Besides, release kinetic analyses were performed in order to compare our experimental release profiles with the current drug release kinetic models. These studies confirmed that these smart nanostructures have the potential to display triggered release profiles for a specific stimulus.