Design and fabrication of novel reactive hydrogels for delivery of therapeutic agents and biomolecular immobilization

Abstract

Polymers have been widely used for the past decades as drug delivery systems owing to their attractive physical, chemical and mechanical properties. In this thesis, nanosized drug delivery systems were developed for the treatment of cancer, owing to their size and ability to target cancer cells via the enhanced permeability and retention effect. Also, cryogels were fabricated as an antibacterial patch and bio-immobilization support by virtue of their macroporous structure. In the first part, nanogels containing hydroxyl and maleimide groups were fabricated using an in-situ polymerization. Nanogels were decorated with doxorubicin, and a thiol-based dye, to act as a marker for imaging. As an improved version, in the subsequent chapter, multifunctional nanogels were fabricated by crosslinking copolymers using their thermo-responsive self-assembly in aqueous media. Obtained theranostic constructs were modified with doxorubicin, a dye and a targeting ligand, and they demonstrated enhanced internalization in breast cancer cells. In the third part, a porphyrin photosensitizer used for photodynamic and photothermal therapy in cancer was used as a crosslinker for fabricating nanogels. Obtained constructs generated singlet oxygen and killed breast cancer cells when excited at certain wavelengths. In the fourth part, furancontaining cryogels were utilized as a wound healing patch for the eradication of bacteria via release of a small molecule antibiotic and anti-microbial peptide, where the former was encapsulated and the latter was attached using the Diels-Alder reaction. Reduced graphene oxide incorporated into cryogels enabled photothermal heating. Upon heating drugs released by desorption from graphene oxide or through retro Diels-Alder reaction eradicated E. Coli and S. Aureus bacterial strains. As a final part of this thesis, novel thiol-reactive cryogels were fabricated and utilized as a platform for bio-immobilization and detection of proteins. In conclusion, various polymeric systems were fabricated and their possible application in different therapeutic areas was demonstrated.