A nose for innovation: Scientists and clinicians unite to rethink schizophrenia treatment

"Many of clozapine’s side effects are peripherally derived, meaning they occur in the body’s organs and systems outside the brain, even though the drug is intended to act in the brain.

“Clozapine’s side-effects can alter the function of the pancreas, the heart, the gut, and the bone marrow, severely impacting the length and quality of a person’s life. Yet, there is no drug-alternative for people who are treatment-resistant."

“How do you avoid the drug hitting the periphery - the gut, the bone marrow, the heart? You deliver it in a more targeted way to the brain through the nose, rather than as a tablet taken orally,”said Professor Darryl Eyles.

Professor Dan Siskind, a long-term research collaborator, agreed. He is an international expert in the treatment of schizophrenia and works clinically as a psychiatrist in Brisbane. He understands only too well the need for a safer, more effective and targeted treatment.

“Clozapine is often the last resort for people with schizophrenia who haven't responded to other medications. For many, it is life-changing – reducing symptoms, hospitalisations, and even suicide risk. But it’s not without risks. Constipation and pneumonia, for example, are the two leading causes of clozapine-related deaths. The drug also carries a tremendous monitoring burden for patients and doctors, with blood tests required before and constantly during its use," said Professor Dan Siskind.

Rethinking clozapine’s delivery: a more direct route to the brain

The team started to explore the idea of not changing the drug but changing its delivery method.

This is where pharmaceutical chemists, Associate Professor Harendra Parekh & Dr Preeti Pandey’s expertise comes in. At UQ’s School of Pharmacy and Pharmaceutical Sciences, A/Prof Parekh and Dr Pandey were experimenting with packaging drugs to deliver them directly to the brain in alternative ways. They developed a novel intranasal formulation of clozapine using their patented method, but before it can proceed to human trials, it needed testing in the lab.

From the chemist back to the lab

With extensive knowledge of the actions of anti-psychotics in experimental animals, Professor Eyles and his team are leading the preclinical studies.

“When administered intranasally to rats, the new formulation achieved high concentrations of clozapine in the brain while significantly limiting its presence in the bloodstream. In addition, we found that the nasal dose required for antipsychotic-like actions was far less than oral clozapine," said Professor Darryl Eyles.

Building on promising preclinical results

The team’s initial findings are limited to animal models in an acute setting; however, they pave the way for further research and future human clinical trials.

Dr Xiaoying Cui and Dr Mia Langguth from the Eyles lab are already testing the longer-term antipsychotic potential of intranasal delivery in rats, as some people take clozapine for life.

Dr Xiaoying Cui explained that alongside these studies, they are conducting more detailed ones examining the drug’s side effects, based on the premise that a lower, more targeted intranasal dose may positively impact peripheral side effects. 

“We have started by studying the metabolic outcomes in rats because they are also susceptible to the development of type 2 diabetes, just like people who take clozapine. We will compare the results for animals who are given clozapine intranasally with those taking the oral dose for the longer-term side effects and metabolic disease," said Dr Xiaoying Cui.

Next step: human trials

Professor Darryl Eyles said they will also test the nasal delivery vehicle in people, checking that it is tolerated and safe. Then, the next challenge is determining the correct dosing for people living with schizophrenia.

“This project is a perfect example of reverse translation, where we have taken clinical observations and built an animal model to better understand the neurobiology. Our hope is that these findings can be forward translated back to the clinic to develop better treatments," said Professor Darryl Eyles.

A new chapter for clozapine

While patients have previously used this drug, they have not encountered it in this form, and clinical trials are required before it can be adopted in practice.

Given its potential to dramatically improve patients' lives, pharmaceutical companies and investors are paying close attention to the intranasal formulation.

The team's findings also underscore the broader potential of advanced drug delivery techniques to enhance outcomes in psychiatric care.

The initial research results are published in Translational Psychiatry.

Professor Eyles' work is funded by The Queensland Centre for Mental Health Research.

This article was first published on The University of Queensland's Queensland Brain Institute News on 7 July 2026.