a PhD position titled: Multiscale modeling of transdermal drug delivery in St. Gallen

Our laboratory. Empa’s Laboratory of Biomimetic Membranes and Textilesaims to develop materials and systems for the protection and optimal performance of the human body. A special focus is to investigate the interactions between materials and human skin, as well as to optimize the protection and ergonomics of systems. The products developed in collaboration with industry are used in the fields of occupational safety, sport and medical applications. We also develop non-invasive materials and systems to help maintain the physical integrity or to relieve pain.

Background. Transdermal drug delivery (TDD) is a non-invasive method to deliver moderately lipophilic drugs with a low molecular weight through our largest organ: the skin. Via this pathway, low-bioavailable pharmacological agents with a high first-pass effect are successfully self-administered in lower doses. A main hurdle with TDD is controlling the level of percutaneous drug absorption since the delivery pathway – the human skin – is patient specific and represents a complex physical and biochemical barrier for many drugs. The absorption kinetics depend on the patient and the bio-environment. Furthermore, the transport pathway – the skin – is a multilayered and multiscale structure, reaching from the thick dermis (≈ mm) down to the lipid bilayers in the stratum corneum (≈ nm). To understand all biophysical phenomena occurring during drug uptake and to control these processes better, the transport at all the different length and time-scales needs a more thorough understanding.

Objective. This project aims to develop a multiscale methodology to gain a deeper understanding in TTD and its control. This implies performing finite-element simulations of transdermal drug uptake, to gain access to the macroscale transport behavior of the drug through the skin. Continuum modeling accuracy is enriched by molecular dynamics (MD) simulations. These lower-scale simulations help us to unveil the behavior of drug molecules at the atomic scale (e.g. in lipid bilayers).

Your tasks

• Develop and apply a multiphysics model of hygrothermal transport in the human skin as well as diffusive drug transport in a transdermal patch and the skin where it is placed on. This model includes drug diffusion, physical adsorption, chemical metabolizing reactions and uptake in the blood flow.
• Develop and perform MD simulations looking into the interactions of several drug molecules with the stratum corneum lipids. The aim is to understand, amongst others, the diffusion and physical binding behavior of molecules, in order to identify the main drivers of the transport process. You will subsequently extract resulting material properties that will be transferred to the macroscale continuum model.
• Use the multiscale approach to better understand and steer TDD for selected drug molecules, and to evaluate the impact of selected TDD enhancers (e.g. chemical, microneedles).

Your Profile

• Completed Master`s degree in engineering, physics or materials science.
• Profound knowledge of diffusive heat and mass transport processes in porous materials.
• Proven experience in continuum modelling (finite element modelling, computational fluid dynamics).
• A strong motivation to learn molecular dynamics simulations and to bridge them with the higher scales (e.g. LAMMPS, GROMACS).
• Experience in programming (e.g. C++, python, fortran) would be beneficial.
• Additional skills and expertise in the biomedical domain are advantageous.
• Excellent communication skills and fluency in English (both written and oral) are mandatory. Knowledge of German is considered advantageous.

Administration. A project duration of 3 years is envisaged to carry out the above research tasks in the form of a PhD thesis. The project is supported by Empa under the supervision of Thijs Defraeye and Riccardo Innocenti Malini, but involves a joint affiliation with ETH Zurich or EPFL. The candidate will perform his research at Empa in St. Gallen. Desired starting date is 1st of April 2019 or upon mutual agreement.