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


   School of Science and Engineering

  ,  Thursday, June 30, 2022  Self-Funded PhD Students Only

About the Project

Overview: 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 disease. 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 effect 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 modeling to complement the practical strands to 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 to 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 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

For informal enquiries about the project, contact Dr Paul Campbell ()

For general enquiries about the University of Dundee, contact

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.

QUALIFICATIONS

Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK in a relevant discipline.

English language requirement: IELTS (Academic) score must be at least 6.5 (with not less than 5.5 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s English language requirements are available online: http://www.dundee.ac.uk/guides/english-language-requirements.

APPLICATION PROCESS

Step 1: Email Dr Paul Campbell () to (1) send a copy of your CV and (2) discuss your potential application and any practicalities (e.g. suitable start date).

Step 2: After discussion with Dr Campbell, formal applications can be made via our direct application system:

Apply for the Doctor of Philosophy (PhD) degree in Physics: Physics : Study : University of Dundee

Please select the study mode (full-time/part-time) and start date agreed with the lead supervisor.

In the Research Proposal section, please:

-       Enter the lead supervisor’s name in the ‘proposed supervisor’ box

-       Enter the project title listed at the top of this page in the ‘proposed project title’ box

In the ‘personal statement’ section, please outline your suitability for the project selected.


Funding Notes

There is no funding attached to this project. The successful applicant will be expected to provide the funding for tuition fees, project specific bench fees and living expenses via external sponsorship or self-funding.

References

In vivo gene silencing following non-invasive siRNA delivery to skin using a novel topical formulation
V Hegde, RP Hickerson, S Nainamalai, PA Campbell, FJC Smith, WHI McLean & DML Pedrioli
Journal of Controlled Release 196, 355-362 (2014)

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