This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 18 studentships for entry in September 2020.
The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities.
Lead supervisor: Dr Begoña Delgado-Charro, Department of Pharmacy & Pharmacology, University of Bath
Co-supervisors: Prof Christopher Bowen (Bath), Dr Albert Bolhuis (Bath), Dr Samuel Bigot (Cardiff) and Dr Emmanuel Brossaeau (Cardiff)
Up to 5 million people in the UK suffer from fungal nail infections (FNI) of toes or fingers at any one time but lack satisfactory treatment. Long oral therapies are relatively successful but cause drug interactions and potential toxicity: a particular concern for elderly, diabetic and immunocompromised patients who have higher incidence of FNI and take other medication.
Local, medicated nail lacquers avoid these problems by applying drugs to the nail only, but have poor efficacy and are advised only for mild infections. FNI is a significant economic burden, causing medical complications and a decreased quality of life to 3-8% of the UK population. Further, given the poor therapy success, recurrence is common and patients undergo repeated treatments. Local treatments fail to deliver sufficient drug to deeper layers of the nail plate where the infection resides. The nail plate is a thick and hard structure, making it very difficult for a drug applied at the surface to permeate across the whole structure. As consequence, effective antifungal concentrations are not attained deep in the nail and the fungi are not eradicated completely.
This project aims to improve FNI therapy by developing microneedles (MN) as a tool to porate the nail plate and create channels through which medication is delivered deep into the nail. We have proof of concept for this approach using a skin poration device, but translation to the clinic requires understanding of the nail poration process to develop a nail-specific MN-based device. Human nails present a hard, complex and curved surface, so developing such a novel device presents a significant micro-engineering challenge. In addition, the flow properties and composition of the medication must ensure it flows deep into the channels.
This interdisciplinary project combines microfabrication, material sciences, drug delivery and microbiology tools to answer the following research questions:
What is the best geometry of the MN?
Which drug formulation works best in combination with the poration approach?
What range of drug concentrations are attained throughout the nail?
Are these drug levels effective?
Can we stop fungal growth?
The mechanical properties of human nail tips as well as the geometry of pores produced with a range of commercially available skin-MN of different materials will be characterized first. Formulations with different flow properties will be applied to porated nails and the distribution of drugs and markers assessed through permeation and imaging experiments. The data will guide the design of the first purpose-made nail MN arrays with different lengths and geometry. Their usefulness will be based on drug level measurements across all sections of the nail and on antifungal effects on a nail infection model. Modelling work will help deciding the optimum number, geometry, and spatial distribution of MN in a final, optimized prototype (IP protection) ready to test in infected nails and patients.
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project.
IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form: https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl
You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding form the DTP will be required to submit an application to study at Bath.
More information on the application process may be found here: https://www.gw4biomed.ac.uk/doctoral-students/
APPLICATIONS CLOSE AT 17:00 ON 25 NOVEMBER 2019.