Combining laser and ultrasound based molecular delivery strategies for enhanced drug delivery

About the project

This project addresses the critical area of delivering therapeutics to the skin. If successful, the approach will have direct and positive consequences for the treatment of a range of skin diseases, but may also be viewed as a more generic means of drug delivery for treating a much wider range of diseases. Given the poor oral bioavailability of many pharmaceuticals, including nucleic acids, the skin represents an attractive target organ for delivery, bypassing the liver, and offering complete accessibility. The main challenge is to achieve efficient and painless passage across the otherwise impenetrable stratum corneum (SC) and subsequently affect dispersal and uptake into the viable cells below. No single system is available at present that achieves this in a reliable way: iontophoresis, electroporation, microneedles, ultrasound, photomechanical effects and superficial laser ablation have been tried with varying success. We are unique in advocating a hybrid approach. The successful candidate will have the opportunity to develop expertise in multiple hardware techniques including ultra-high-speed imaging, thermal imaging, patch-clamp electrophysiology, confocal/scanning probe microscopies, and flow cytometry, as well as the full range of biological assaying, approaches. There will also be a need for mathematical modelling to complement the practical strands of the project. It is anticipated that this multi-disciplinary skill-set will be highly attractive to a wide range of potential downstream employers. A candidate with a strong aptitude for challenging hands-on experimentation, bolstered with solid analytical skills, is sought and applicants with a background in Physics or Biomedical Engineering would be especially welcome.

Physics driven drug delivery

We intend to assess, develop, and optimise ablative fractional resurfacing (AFR) of skin, in order to achieve drug delivery of our target therapeutics. AFR is a novel laser procedure that has recently received favourable reviews for its efficacy and safety in aesthetic contexts. The procedure itself essentially consists of a series of energetic laser shots each undertaken with a tight spot focus, creating microscopic vertical ablated channels in the skin that are surrounded by a thin layer of coagulated tissue. Ablation of the SC in this controllable fashion has led to its exploitation for molecular delivery of topical drugs within the past few years, thereby de-risking this present study. Thermal collateral damage is controlled chiefly by limiting laser pulse widths, however, we will monitor and optimise this process in real-time using thermal imaging, whilst developing a Franz diffusion cell to track molecular transport across the compromised skin. The tissues will also be subjected to low amplitude pulsed ultrasound in order to force dispersal of the molecular therapeutics towards the sub-dermal target plane. A critical aspect of the study will thus be to optimise the laser parameters to control the extent of coagulation, limit thermal collateral damage, and ensure the tissue plane is left in a state that predisposes it to a significant update of therapeutic molecules. Ascertaining the optimized downstream ultrasound field parameters that best disperse siRNA is a second critical objective. This will provide a firm platform for a practical clinical translation.

Diversity statement

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.