Dynamic Hybrid CB[8]-hydrogels for Delivery of Chemotherapy against Glioblastoma

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Glioblastoma (GB) is one the most devastating brain tumours accounting for 50% of all types of brain cancers in humans. Standard treatment involves tumour resection followed by radiotherapy and concomitant administration of Temozolomide as chemotherapeutic agent. The presence of the blood-brain barrier (BBB) limits the brain penetration of the majority of systemically administered chemotherapeutic drugs, accompanied by peripheral tissue toxicity. Injectable, self-healing and mechanically tuneable hydrogels have been designed and pioneered within the Scherman group to match the mechanical properties of the contiguous human tissue, representing a new treatment methodology for aggressive brain tumours that overcome many of the pitfalls associated with the current state-of-the art treatment. These dynamically crosslinked supramolecular hydrogels are designed to deliver chemotherapeutic drugs in a spatiotemporally controlled manner for the treatment of GB and prevent tumour recurrence. For the development of dynamic hybrid hydrogels, different formulations of nanoparticles (mesoporous, polymeric) will be employed and subsequently be encapsulated within the hydrogel matrix to tailor and prolong the drug release profile. The size of nanoparticles, drug loading capacity and their degradation kinetics will be explored in order to optimise this hybrid formulation. Investigation of mechanical properties of these hybrid gels and degradation/stability studies will be performed to identify the optimal nanoparticle/gel ratio. In vitro and in vivo biocompatibility of the designed gels will also be evaluated on primary GB cell lines.