Degradable hydrogels for local drug delivery

Abstract

Hydrogels are widely utilized in biomedical applications owing to their controllable physical and chemical properties. Their physical strength, elasticity, porosity, water uptake capacity, degradability and biocompatibility can be tuned according to the application of interest. Tunability of the final properties makes them useful constructs for cancer related applications such as tumor models, diagnostic systems and smart drug delivery platforms. The aim of this thesis was to obtain stimuli-responsive degradable hydrogels for local drug delivery in cancer therapy. For this purpose, a functionalizable copolymer, poly(PEGMEMA-co-SCEDEMA), was synthesized via RAFT polymerization. Hydrogel formation was achieved by crosslinking this copolymer with PEG-diamine through a disulfide-based redox and carbamate-based acid sensitive linker. In order to show the tunability of physical properties, PEG-based crosslinker length was chosen as variable. Hydrogels were shown to have lower physical strength but greater porosity and water uptake with increasing crosslinker length. This also had a considerable impact on degradation rate which was expected to influence drug release behavior. To examine this, DOX was chemically bound to hydrogels via the same dual stimuli responsive, disulfide and carbamate bearing side chain which was also utilized for crosslinking as well. Dual-responsive hydrogels were desired in order to introduce a tumor environment sensitive character into hydrogels. This responsivity was designed considering the slightly acidic and reducing conditions of tumor environment. Drug release was investigated under physiological (pH = 7.4), acidic (pH =5.5) and GSH containing acidic environment. As expected, sustainable release of DOX was achieved reaching around 80% cumulative release under GSH containing acidic conditions accompanied by the total degradation of hydrogel construct.