Novel functional hydrogels and polymer coated magnetic nanoparticles with degradable linkers for biomedical applications

Abstract

In this thesis, the design and fabrication of novel reactive interfaces such as hydrogels and polymer coated nanoparticles were investigated for applications related to the delivery of therapeutic agents. Randomly crosslinked hydrogels incorporating amine and thiol reactive groups that allow conjugation of various bioactive molecules in a releasable fashion were synthesized. Apart from using novel modes of conjugation and release from non-degradable hydrogel scaffolds, synthesis of a new class of degradable hydrogels with well-defined network structure was also established. Effective thioldisulfide exchange reaction based strategies were used to synthesize hydrogels where the crosslinked density could be changed and protein release profiles could be modulated. Importantly, very fast and complete degradation of these hydrogels to release the encapsulated protein was achieved. The first project involves preparation and functionalization of the amin reactive poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels. Obtained activated carbonate containing 3D networks were evaluated as slow releasing drug reservoirs. In the second project, preparation of stimuli responsive welldefined polymeric networks with disulfide linkers was proposed. Hydrogels fabricated by different moleculer weight polymer were investigated in terms of their encapsulation and degradation behavior. In the third study, synthesize of cyclodextrin containing well-defined hydrogels and release behavior through thiol-disulfide exchange reaction were reported for controlled drug release application. In the fourth study, fabrication of functional hydrogels with dual functional monomers was demonstrated and functionalization and release studies were performed. In the final study, novel functionalizable polymer coated hydrophilic magnetic nanoparticles that contain thiol-reactive polymeric coatings were prepared via a „graft-from‟ approach to design pyridyl disulfide containing polymer coated magnetic nanoparticles.