The Development of Implantable Anti-tumour Devices for Enhanced Efficacy of Repurposed Drugs Using Advanced Manufacturing

Drug repurposing or repositioning, which investigates new indications for approved drugs, has always been a core approach in drug development, with approximately 30-40% of new drugs and biologics approved by the US FDA between 2007 and 2009 being repurposed or repositioned products (DOI: 10.1358/dnp.2010.23.1.1440373).  Following the FDA’s emergency use authorisation (EUA) of several repurposed drugs, including ivermectin, hydroxychloroquine, remdesivir, azithromycin, to treat Covid-19, repurposed medicines have received further heightened attention.  

Amongst different categories of repurposed anti-cancer agents, the anti-helminthic benzimidazoles have demonstrated promising in-vitro and in-vivo activity against a variety of malignancies including leukaemia, ovarian, breast, liver, colon, lung, prostate, head and neck cancers.  

These compounds exhibit poor aqueous solubility, are subject to extensive first-pass metabolism in the liver (1-5% in humans), and give rise to severe side effects such as neutropenia due to myelosuppression when high doses are administered for a prolonged time. Naturally, this precludes their widespread application in cancer treatment.   

The overarching aim of this project is to achieve enabled drug performance, thus enhanced anti-tumour efficacy and reduced dosing, of benzimidazole drugs using novel implantable devices, prepared via advanced manufacturing.  

Key objectives of the project include: 

• Identification of effective drug-enablement technologies applicable to the chosen candidate drug(s).
• Formulation and extensive characterisations of drug-enabling matrices using implantable materials.
• Confirmation of anti-tumour activity of the prepared formulations, through comparison to the native drug and the commercially available products using in-vitro cytotoxicity assays.
• Establishment of the quality control protocols for these implantable devices through the use of Process Analytical Technology (PAT) tools and chemometric data analysis.

Subject area 

Pharmaceutics 

Pharmaceutical Engineering 

Pharmaceutical Science 

Candidate requirements / Key skills required for the post  

This project requires an undergraduate student that has a background in one of the following subject areas: 

• pharmaceutical sciences
• pharmaceuticals
• pharmaceutical engineering
• chemical engineering
• pharmacy

Knowledge and/or experience of the following technical skills/knowledge would be beneficial: 

Hot-Melt Extrusion (HME) – twin-screw extrusion, process optimisation and machine configuration. 

Thermal Analysis – Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). 

In-vitro anticancer activity tests – In-vitro cytotoxicity assays, Western Blots 

Other Analytical Techniques – polarized light microscopy (PLM), X-ray powder diffraction (XRPD), drug dissolution, UV-Vis, HPLC-UV, IR and Raman spectroscopy, QbD 

Modeling and Simulation – Applying empirical models and using simulation software. 

Laboratory Techniques – Preparing samples, analysing data, documenting procedures and presenting findings. 

How to apply / contacts 

Postgraduate Research applicants must have applied to Queen’s, via the Direct Applications Portal. 

https://dap.qub.ac.uk/portal/user/u_login.php  

Relevant links / more information  

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/PostgraduatePositions/ 

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/ 

Training provided through the research project 

The successful student will join a multidisciplinary research team that will equip them to work within the Pharmaceutical Industry or to pursue a career in academia. The student will gain a range of skills in manufacturing and analytical techniques that are of most relevance to the current pharma industry. The student will also work alongside academics from other Schools (E.g., Chemistry and Chemical Engineering, and Mathematics) to build appropriate models and simulations to assess risk. 

Importantly, the student will develop their ability to critically evaluate scientific literature, formulate research questions, collect and analyse data, and interpret complex data using various statistical and other relevant tools. 

In addition, students will also be taught how to manage a research project from conception to completion, including setting objectives and associated timelines.  

Upon completion of our training, they will achieve enhanced scientific writing and presentation skills, whilst also gaining an opportunity to work in a multidisciplinary team and build professional relationships through conference/seminar attendances.