Formulations for Convection-Enhanced Delivery of Therapeutics in Diffuse Intrinsic Pontine Glioma

Convection-Enhanced Delivery (CED) is a technique in which a direct infusion of drugs to the specific and difficult to reach areas of the brain is achieved via small catheters implanted surgically. CED has been applied to a number of neurological conditions, including a suite of brain tumours and neurodegenerative diseases. The issue of infusate backflow associated with many commercially available catheters means that drug solution volume delivered via this method is limited. As a result, high concentration bolus injections of chemotherapeutics are used, and local off-site neurotoxicity is a consequence of rapid drug diffusion away from the tumour site.
We hypothesise that formulating drugs into long-acting infusates capable of forming intratumoural depots will lead to lower off-target toxicity and better treatment outcomes. Whilst reformulating drugs for CED is applicable to a number of diseases, in this project, formulations will be targeted towards Diffuse Intrinsic Pontine Glioma (DIPG), an aggressive paediatric brain tumour which is inoperable and for which current treatment options are poor. This project will aim to understand how to rationally formulate APIs for delivery via CED, with a focus on delivery of treatments for DIPG.

The following aims are priorities for this project:
- Understanding of formulation properties for local and extended persistence at the tumour site when administered via CED
- Generation of formulations with minimal backflow when administered through CED

Project outcomes will be an understanding of how to formulate APIs for general administration via CED, and specific formulations that can be applied to CED in DIPG.