Coaxial hydrogel structures for drug delivery to tumors

Biopolymer-based hydrogels have emerged as promising platforms for drug delivery systems (DDSs) due to their inherent biocompatibility, tunable physical properties and controllable degradability. Yet, drug release in majority of these systems is solely contingent on diffusion of drug molecules through the hydrogel, which often leads to burst release of drugs from these systems. As a result, the main aim of this thesis was to develop suitable hydrogel platforms that allow sustained release of anti-cancer drugs, to be ultimately used as implants for local delivery of drugs to tumors. To this end, inspired by the chemistry of mussel adhesive proteins, a new generation of coaxial hydrogel structures were developed that could simultaneously exert both affinity and diffusion control over the release of chemotherapeutic drugs. Specifically, dopamine-modified hydrogel along with chemotherapeutic drugs was used as the main core component to confer affinity-controlled release, while a methacrylated hydrogel was used as the shell composition to provide the controlled diffusion barrier. Initially a well-recognized wet-spinning technique was employed to fabricate coaxial fibers with the given composition, mainly because this fabrication method allows high throughput and continuous production of coaxial structures. Accordingly, it was shown that the fabricated coaxial fibers were robust in both dry and wet conditions, and most importantly they were capable of exerting a controlled release of Doxorubicin (a chemotherapeutic drug) over a span of 3 weeks. Also, in vitro and in vivo evaluations showed that drug loaded coaxial fibers had optimal anticancer activity against pancreatic cancer cells...