Up to 5 million people in the UK are affected by fungal infection of toe and fingernails (ONC) at any one time, with a concerning high prevalence in elderly, diabetic and immunocompromised patients. Untreated ONC reduces quality of life and is a source for secondary foot infections increasing risk of ulcerations and amputations, adding to the burden on healthcare systems. Further, treatment failures are frequent with recurrence being ~ 50% due to lack of mycological cure and reinfections.
Behind this unmet medical need are a poor understanding on how fungal colonization occurs, its dynamics during antifungal treatment and the failure of medicated nail lacquers to provide effective drug concentrations across the whole thick keratin plate.
This project will employ advanced imaging techniques (Raman spectroscopy, MS, two-photon fluorescence imaging), material characterization (mechanical properties, nanoindentation) and formulation tools, microbiological tests, and donated nail-clippings to design a novel, cost-effective, patient-activated medical device combining a micro-poration component with purpose-designed formulations of antifungals to overcome the limited efficacy of current therapies by optimizing antifungal bioavailability at the infection site.
The team has established proof-of-concept1-3 that drug diffusion occurs from reservoirs localized in created pores, with sustained drug delivery potentially enabling fortnightly rather than daily, therapy. Nevertheless, proof-of-concept data was obtained with skin micro-poration devices not optimized for the nail plate.
The project will comprise the following stages:
a. Design and develop a poration device that adapts to the nail curvature and creates pores into which formulations, specifically developed for this purpose, will be delivered.
b. Use advanced imaging, material characterization and in vitro permeation tests to establish the optimum geometry, number and distance between microneedles that ensures efficacious levels of drug across the nail plate whilst maintaining nail integrity4.
c. Develop a model for nail fungal infection5-6 to elucidate the stages of fungal colonization, the response to treatment and failure modes. In addition to microbiological tests, non-invasive imaging techniques will enable in real time, non-invasive elucidation of changes in the fungal biomass, the nail components and structure, during antifungal therapy to establish key attributes and specifications for the new medical device.
Candidates with a strong science (physics, pharmaceutics, microbiology) and/or engineering background are invited to apply to this challenging and original PhD project that aims to develop a new medical device to treat fungal nail infections. These infections occur in 10% of the population yet, are difficult to treat. This research will develop interdisciplinary skills and will provide a holistic view on the process of developing medical devices that can tackle this problem. Spectroscopy imaging will be used as a tool to understand fungi-nail-drug interactions as well as to characterize the process of poration and drug diffusion across the nail plate.
This interdisciplinary PhD project will develop and integrate your advanced imaging, microfabrication, material sciences, drug delivery and microbiology skills to engineer microporation medical devices that will create micro-channels in the nail plate through which specifically formulated medication will be delivered deep into the nail to reach effective concentrations of antifungals.