Gut-Targeted Nanomedicines for Overcoming the Metabolic Side Effects of Antipsychotics

About this project 

The objective of this project is to develop a bespoke nanomedicine that mitigates the metabolic side effects of two commonly prescribed antipsychotic drugs: olanzapine and clozapine. We hypothesise that formulating antipsychotics with a drug delivery vehicle that targets the gut microbiome will prevent key metabolic side effects, including weight gain and hyperglycaemia, while also increasing therapeutic efficacy by modulating the gut-brain axis. The supervisory team will build on their previous collaborative research where they engineered prebiotic-coated lipid nanoparticles (PreLNPs) for the improved delivery of the antipsychotic, lurasidone. While pilot studies demonstrated proof-of-concept, further work is clearly required to optimise the structure, composition, and activity of PreLNPs for improving the safety and efficacy of antipsychotics, especially for those that suffer from more significant side effects and are more commonly prescribed. The project will be investigated in 3 phases:
1. Formulation development and characterisation: a catalogue of InuLNPs with varying compositions and structures will be synthesised using an advanced microfluidic fabrication approach and characterised using specialised physicochemical characterisation approaches.
2. In vitro evaluation: Drug delivery characteristics of InuLNPs will be determined using conventional pharmaceutical evaluations and drug-microbial interactions will be assessed using in vitro monoculture assays.
3. In vivo studies: The pharmacokinetic performance, metabolic side effects, and efficacy of InuLNPs will be investigated in a preclinical schizophrenia animal model for both olanzapine and clozapine. The model has been developed in-house by A/Prof Schwartz (CCB) and will enable structure-activity relationships to be determined for evaluating the optimal InuLNP composition for maximising antipsychotic safety and efficacy.

What you’ll do 

Outcome 1: The preclinical studies performed in this project will provide the critical evidence needed to advance the proprietary gut-targeted nanomedicine towards clinical and commercial translation. UniSA Ventures manage the intellectual property related to this project through a patent protecting PreLNPs. The inclusion of a psychiatrist (Dr Natalie Mills) and pharmaceutical manufacturer (Pharmako) on the research team ensure the clinical and commercial feasibility of the project.

Outcome 2: The new nanomedicine will overcome the leading cause of antipsychotic non-adherence (i.e., metabolic side effects) and increase therapeutic efficacy by targeting the gut-brain axis, presenting transformative treatment outcomes for the 700,000 Australians living with schizophrenia and bipolar disorder. Healthcare benefits will extend beyond schizophrenia, given over 30% of antipsychotic prescriptions are ‘off-label’, including for the treatment of depression and anxiety. Critically, antidepressants also trigger debilitating metabolic side effects through disruption to the gut microbiome, and thus, successful project completion will lead to new applications for the nanomedicine platform across different mental illnesses.

Outcome 3: The high-level training of a PhD student within an interdisciplinary research environment will facilitate skill development and excellent graduate opportunities within academia and industry. The student will be trained in a range of pharmaceutical formulation and evaluation (including in vitro and in vivo) techniques and they will disseminate their findings through journal publications and presentations in both scientific, industry and clinically focused conferences. The candidate will engage with Pharmako Biotechnologies (end-user) through research internships where they will be trained on scale-up pharmaceutical manufacturing, which will be invaluable to the student and will strengthen this established and valuable collaboration.

Where you’ll be based 

The project directly aligns with the Centre for Pharmaceutical Innovation’s objective, to ‘develop novel pharmaceutical and nutraceutical products that address unmet clinical and commercial needs’ through an enterprising and collaborative approach (Strategic Priorities 3 & 4, Academic Enterprise Plan). The project is strategically aligned to address the National Science and Research Priorities by ‘improving physical and mental wellbeing’ (Priority 2: Supporting healthy and thriving communities). By partnering with Pharmako, the project addresses the Australian Industry Growth Centres Initiative of ‘increasing collaboration and commercialisation’ in ‘advanced manufacturing’ and future ‘medical technologies and pharmaceuticals’.

The supervisory team brings together complementary skilled researchers with the multi-disciplinary experience required for this project, highlighted through strong track records in the fields of pharmaceutical science, psychiatry, and gut health. Dr Paul Joyce, an emerging MCR (>70 publications; 85% Q1 journals) with critical expertise in nanomedicine engineering, drug-gut microbiome interactions, and preclinical animal models will lead the research team as principal supervisor. Dr Joyce is a current Hospital Research Foundation Fellow (2023-26) and currently supervises 11 PhD students (6 principal supervisor), having completed 6 HDR graduates. This project directly aligns to his current fellowship and future fellowship applications (e.g. NHMRC Investigator 2026). This project will therefore build critical capacity and ensure the success of each fellowship by enabling Dr Joyce to continue his pioneering work within the area of antipsychotic nanomedicines. Importantly, this scholarship provides further opportunity for Dr Joyce to advance his growing independence and leadership within the field of nanomedicine. Financial Support  

This project is funded for reasonable research expenses. Additionally, a living allowance scholarship of $35,200 per annum is available to Australian and New Zealand citizens, and permanent residents of Australia, including permanent humanitarian visa holders. Australian Aboriginal and/or Torres Strait Islander applicants will be eligible to receive an increased stipend rate of $52,352 per annum (2025 rate). A fee-offset or waiver for the standard term of the program is also included. For full terms and benefits of the scholarship please refer to our scholarship information. International applicants are not invited to apply at this time.

Eligibility and Selection 

This project is open to applications from Australian or New Zealand citizens, and Australian permanent residents or permanent humanitarian visa holders. International applicants are not invited to apply at this time.

Applicants must meet the eligibility criteria for entrance into a Master of Research or a PhD. Additionally, applicants must meet the project selection criteria: 

• A relevant undergraduate degree in Laboratory Medicine, Pharmaceutical Science, Pharmacy, Biomedical Science, or similar.
• Strong written and verbal communication skills.

All applications that meet the eligibility and selection criteria will be considered for this project. A merit selection process will be used to determine the successful candidate.

The successful applicant is expected to study full-time and to be based at our City West Campus in the heart of Adelaide. 

Essential Dates 

Applicants are expected to start in a timely fashion upon receipt of an offer. Extended deferral periods are not available. Applications close on Friday 7 March 2025.