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

Lead Research Organisation: University of Cambridge
Department Name: Chemistry

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513180/1 01/10/2018 30/09/2023
2459143 Studentship EP/R513180/1 01/10/2020 31/03/2024 Saif Baquain
EP/T517847/1 01/10/2020 30/09/2025
2459143 Studentship EP/T517847/1 01/10/2020 31/03/2024 Saif Baquain
 
Description The gel is aimed to target patients with Glioblastoma, a form of brain cancer. The gel can be applied locally during resection to release chemotherapeutic drugs to prevent recurrence of the disease. Furthermore, as the drugs are released locally, this enhances their efficacy and reduces the propensity of side-effects which improves patient outcomes. The hydrogel has been shown to be biocompatible and biodegradable. Specifically, my work is focused on increasing the drug loading capacity of these gels and exploring release of multiple drugs to understand synergistic effects. I am looking at increasing drug loading through the addition of high-capacity vehicles within the gels (e.g. nanoparticles) and studying how to augment and control release profiles of various drugs out of these gels.
Exploitation Route The main goal of this award is to establish a local drug delivery formulation for the treatment of Glioblastoma. Therefore, the direct application of this system would involve the implantation of this device following surgery in the tumour cavity to release chemotherapeutic drugs. This approach would allow for the eradication of any remaining cancer around the tumour to prevent the recurrence of this disease. Furthermore, a host of drug molecules can be loaded within the hydrogel which makes it an excellent candidate for the treatment of multi-drug resistant diseases and expands its application in the field of biomedical devices. We envisage that due to the nature of this gel (biocompatible, injectable and self-healing), the hydrogel would be compatible for use within other organs e.g. lungs, liver and pancreas among others to treat cancer and a variety of other diseases. The characteristics of this hydrogel also make it useful in a variety of other biomedical applications including medical imaging, cell entrapment and adhesives.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology