2025 RTP round - Brain Delivery of Itraconazole for the Treatment of Glioblastoma.

Updated: 14 days ago
Location: Perth, WESTERN AUSTRALIA

Status: Closed

Applications open: 1/07/2024
Applications close: 18/08/2024

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About this scholarship

 

Project Overview

Glioblastoma (GBM) is the most malignant primary brain tumour, representing approximately half of all primary central nervous system malignancies. It is a rapidly developing tumour seen in patients with an average age of 65 at diagnosis, with a median overall survival of 15 to 16 months following tumour detection. Long-term survival is rare, with less than 5% of patients typically surviving for five years or more following diagnosis. GBM presents a significant difficulty as a brain tumour with very limited response to standard treatments and a high recurrence rate. Treatment options are severely restricted once the tumour recurs. Immunotherapeutic methods have been successful in treating several solid tumours but have limited efficiency against GBM.  


The Sonic Hedgehog (HH) pathway plays a crucial role in embryonic development, tissue regeneration, and stem cell maintenance. Unregulated activation can lead to various illnesses, including immunological dysregulation, infections, and the development and advancement of different types of malignancies such as basal cell carcinoma, medulloblastoma, pancreatic cancer, breast cancer, small-cell lung carcinoma and GBM. Itraconazole, an antifungal drug, demonstrates promise in pre-clinical studies for its ability to prevent tumour growth by targeting the Sonic Hedgehog (HH) receptor, which is a different mechanism than its antifungal action. Itraconazole affects the crucial HH pathway element Smoothened (Smo) in a way that differs from cyclopamine and other Smo inhibitors. However, its limited water solubility impedes achieving adequate drug concentrations across the blood-brain barrier (BBB) to reach the brain tumour. 


This research project consists of three stages. The first stage involves the development and characterization of itraconazole-loaded drug delivery system (DDS). Based on the existing findings on BBB, develop and optimize DDS for itraconazole delivery. Potential DDS options are liposomes, polymeric nanoparticles, and inclusion complex formation. DDS characterization for parameters like particle size, surface charge, drug loading capacity, and in vitro release profile. The second stage involves in vitro cell culture studies using GBM cell lines (e.g., U87-MG) to assess the antiproliferative effects of the itraconazole DDS. Additional DDS optimization may be pursued depending on the outcomes of the in vitro experiments. The third stage will involve in vivo studies on animal models of glioblastoma to evaluate the effectiveness of the selected DDS in tumour growth inhibition, survival rate, biocompatibility and brain targeting efficiency.

 

Aims

• Develop a novel and effective brain delivery system for itraconazole. 
• Demonstrate the therapeutic potential of itraconazole delivery system for glioblastoma treatment. 
• Provide pre-clinical data to support the advancement of this approach towards clinical trials.

 

Objectives

• This research project aims to develop a safe and efficient method for delivering itraconazole to the brain to treat glioblastoma.

 

Significance 

• This research project has the potential to significantly improve the treatment of glioblastoma by offering a new therapeutic strategy with improved drug delivery to the brain tumour. If successful, it could lead to better patient outcomes and improved survival rates. 
• Itraconazole repurposed for cancer treatment has the potential to enhance the affordability of this medication for cancer patients in low- and middle-income nations.

 

The international research collaboration team possesses the necessary skills for the proposed study project. 
• Formulation science: Dr. Victor Chuang from Curtin University. 
• Pharmaceutical analysis: Professor Kevin Batty from Curtin University 
• Cell culture investigations: Professor Yu Ishima from Kyoto Pharmaceutical University 
• Animal experiments: Professor Kazuaki Taguchi from Keio University 
The research laboratories in buildings 306 and 308 have equipment for DDS production and characterization, including Mastersizer, Zetasizer, and HPLC. 
This project complements the School’s overall research profile in pharmaceutical sciences and pharmacology (top 200 in QS world ranking for pharmacy and pharmacology), and extends our collaborative research arrangements with colleagues in Japan. The project will provide significant outcomes related to novel formulations for delivery of azole drugs to the brain.
 

An internship may be available for this project. A short-term attachment at a hospital or a pharmaceutical manufacturing company in Australia or overseas in Japan or Malaysia can be organised depending on the candidate's interest.


  • Future Students

  • Faculty of Health Sciences

  • Higher Degree by Research

  • Australian Citizen
  • Australian Permanent Resident
  • New Zealand Citizen
  • Permanent Humanitarian Visa
  • International Student

  • Merit Based

The annual scholarship package, covering both stipend and tuition fees, amounts to approximately $70,000 per year.

In 2024, the RTP stipend scholarship offers $35,000 per annum for a duration of up to three years. Exceptional progress and adherence to timelines may qualify students for a six-month completion scholarship.

Selection for these scholarships involves a competitive process, with shortlisted applicants notified of outcomes by November 2024.


Scholarship Details

1


All applicable HDR courses.


We are looking for a self-motivated PhD candidate with excellent organisation, problem-solving and laboratory skills in pharmaceutical science or pharmacology or a closely related area. Candidates with strong quantitative skills, including familiarity with research methodologies, data analysis, and statistical tools are desired for this project.  A solid understanding of pharmaceutical sciences, including relevant wet laboratory work experience, ready or able to do cell culture and animal studies, are essential. The applicant should also demonstrate strong technical writing skills. Possessing proficiency in the Japanese language would be beneficial. Must be eligible to enrol in PhD programs at Curtin.
 


Application process

Please send your CV, academic transcripts and brief rationale why you want to join this research project via the HDR Expression of Interest form to the project lead researcher, listed below. 


Enrolment Requirements

You must be enrolled in a Higher Degree by Research Course at Curtin University by March 2025.


Enquiries

Project Lead: Dr Victor Chuang



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