Investigating a new way of delivery drugs to the site of childhood brain tumours

Central nervous system (CNS) tumours are the major cause of cancer related death in children, with high grade invasive brain tumours showing a poor response to treatment and often recurring in the same place despite multiple types of treatment.

Conventional oral or intravenous chemotherapy distribute drugs to the whole body but cause toxicity to healthy parts of the body (e.g. bone marrow failure), which limits the maximum dose that can be achieved in the brain. This presents a particular concern for CNS tumours where the blood-brain-barrier (BBB) restricts drug influx from the circulation. The ability to deliver chemotherapy locally at the tumour site offers the opportunity to target residual cancer cells post-surgery whilst reducing toxicity to healthy parts of the body.

Our laboratory has developed a biodegradable polymer paste called PLGA/PEG, which several chemotherapy drugs can be mixed into, prior to the paste being moulded to the tumour cavity lining after surgery. It is important that we can observe whether the drugs released from PLGA/PEG actually get to where any remaining brain cancer cells are. Currently the only way to measure the distribution of drugs in the body is to inject radioactive drugs into an animal. The animal is then killed and the location of the drug in the body is worked out by measuring radiation. This unfortunately requires a high number of animals, is a method that cannot measure different drugs at the same time and the radioactive labelling of a drug may mean that the movement of the drug (pharmacokinetics) differs compared to the non-labelled drug that a patient may receive.

This study aims to develop a model in the laboratory to measure how far chemotherapy drugs released from PLGA/PEG paste can move through slices of brain. As we can use several slices of brain from just one animal, this will dramatically reduce the amount of animals needed for this type of research. At different time-points we will measure how far the drugs released from PLGA/PEG have moved across the brain slice.

By taking measurements of six chemotherapy drugs across a number of time-points, we hope to develop a mathematical model that can predict the movement of other drugs through brain tissue. The model could also quickly identify drugs that do not penetrate into brain tissue very well and which therefore should not be taken forward for clinical trials in children.

Completion of a successful project will allow the developed methods to be used to retrospectively measure drug distribution in animals with brain tumours. Ultimately the work will enable the selection of drugs released locally from PLGA/PEG at the site of childhood brain tumours that have been removed surgically, which have the greatest chance of effectively targeting residual cancer cells in the patient and likely inform drug delivery considerations via other methods.