The project explores a new method to bypass the brain’s natural shield (the blood-brain barrier) and deliver drugs right to the tumour and at the exact dose needed to treat the cancer. The team has already proven this method successful; and this project is the last step before we can help pipeline this to early phase clinical trial for brain cancer patients.

This is the first project to develop a nasal spray to non-invasively deliver drugs to the brain. It pairs several technologies – nanoparticles which house the drug – focused ultrasound and microbubbles which directs the drug containing nanoparticles to where they need to go in the brain – all via delivery through the nose.

Drug therapy for brain cancer is challenging because the blood-brain barrier makes it difficult for drugs to penetrate and accumulate at the right dosage needed to have an effect. This potential new method provides a non-invasive and effective way to get the drugs right to where they need to be working.

Focused ultrasound-mediated intranasal delivery for non-invasive drug delivery to the brainstem with minimised systemic exposure in a large animal model

Diffuse midline gliomas (previously known as diffuse intrinsic pontine glioma) is the deadliest paediatric brain cancer that often occurs at the brainstem. It has a median survival from the time of diagnosis of only 9 months and 100% mortality rate, a dismal prognosis that has remained unchanged over the past 40 years.

To address the unmet and urgent need for innovative technology to improve diffuse midline glioma treatment, this project proposes to develop a novel drug delivery technique – focused ultrasound -mediated intranasal delivery (FUSIN). FUSIN utilises the intranasal route for direct nose-to-brain drug administration, thereby bypassing the blood-brain barrier and minimising systemic exposure. FUSIN also utilises focused ultrasound to induce microbubble cavitation (expansion and contraction of microbubbles) within the focused ultrasound focal zone, leading to enhanced transport of intranasal-administered agents to the focused ultrasound -targeted brain location.

Compared with currently available techniques, FUSIN is unique in that it can achieve non-invasive and spatially targeted brain drug delivery while minimising toxicity in other organs. Our previous studies already demonstrated successful delivery of various agents to different brain locations using FUSIN in a mouse model. The objective of this application is to evaluate the feasibility and safety of FUSIN to obtain compelling preclinical evidence needed to support an early phase clinical trial.