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  Development of antifungal nanotherapeutics containing AmB+ drug combinations using an advanced continuous manufacturing technology

   School of Pharmacy

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  Prof Gavin Andrews, Prof Brendan Gilmore  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Each year there are more than 150 million severe cases of fungal infection that occur globally, resulting in significant mortality. Latest estimates suggest that there are approximately 1.7 million deaths annually, with current predictions pointing to a continued increase in incidence and fatality rates. Coinciding with this, there are also significant and well-placed concerns around the emergence of drug resistant fungi, most notably as a result of long-term application and prophylactic use of anti-fungal drugs. In October 2022, the World Health Organisation published the Fungal Pathogen Priority List (FPPL), divided into three categories: critical, high and medium priority pathogens, considering their unmet research and development needs and highlighting their increasing clinical importance. Not only do invasive fungal diseases pose a life-threatening problem, particularly for immunocompromised patients, their increased incidence has a major impact upon health care systems due to high associated costs, estimated to be £25-40K per patient. Despite the availability of effective antifungal drugs, treatment of fungal disease is limited by high antifungal drug product cost, toxicity, emergence of antifungal resistance, and limited spectrum of action. Amphotericin B (AmB), despite a long history of use, has potent, broad spectrum fungicidal activity and a favourable resistance profile, however its toxicity, and cost restrict its wide-ranging application.

Over the last 10-years Professor Andrews has led a team that have developed a novel manufacturing method capable of continuously producing nano-based drug carriers, more recently for enhancing drug solubility and development of AmB nano-carrier systems. Professor Gilmore has extensive experience in the development and application of biofilm susceptibility models (including fungal and fungi-bacteria mixed species biofilms) for discovery/evaluation of novel anti-biofilm compounds and technologies, evolution of resistance, and techniques for enhancement of antimicrobial delivery to microbial biofilms to circumvent biofilm tolerance to antimicrobial challenge.

In this project, we intend to overcome current challenges associated with the broad use of AmB by manufacturing low-cost nanocarrier-encapsulated anti-fungal drug combination products with improved antifungal and antibiofilm activity. Our current project extends significant investment from SFI, NSF, InvestNI, and the MRC in this interdisciplinary field. The perspective PhD students will work within this dynamic, multidisciplinary team to develop innovative scalable processing platforms for affordable antimicrobial nanotherapeutics involving the screening of a AmB+, with a particular focus on repurposing off-patent compounds that offer synergistic antifungal activity.

Home applicants must meet the following academic criteria:

1st or 2.1 honours degree in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, or a closely related discipline.

International applicants must meet the following academic criteria:

IELTS (or equivalent) of 7.0, a 2.1 honours degree (or equivalent) and a master’s degree in a relevant subject.

Biological Sciences (4) Engineering (12) Medicine (26)

 About the Project