PhD defence by Nanna Wichmann Larsen

On Wednesday 5 July 2023, Nanna Wichmann Larsen will defend her PhD thesis "Development of high-throughput screening assays for oral peptide drug delivery".

Time: 13:00

Place: Building 341, auditorium 22 & zoom: https://dtudk.zoom.us/meeting/register/u5ErfuCoqzopHdR_ukcLTBQjzwyV9LD0N_W8

Please be aware that the PhD defense may be recorded - This will also be informed at the beginning of the PhD defense.

Principal supervisor: Professor Niels Bent Larsen

Co-supervisor: Professor Thomas Lars Andresen

Associate Professor Jens Bæk Simonsen

Researcher Kasper Kristensen

Assessment committee:
Associate professor Line Hagner Nielsen, DTU Health Tech
Professor David Brayden, University College Dublin
Professor Hanne Mørck Nielsen, University of Copenhagen

Chairperson:
Senior Researcher Jannik Larsen, DTU Health Tech

Abstract:
Imagine you are to take medications for the rest of your life. Now imagine that this needs to be done through eg. regular injections. That is for many people the case today. Yet, the preferred way of taking medications is by swallowing a tablet. For peptide drugs, such as insulin, this is, however, rarely possible. A major obstacle is that such drug molecules are too large to cross the lipid bilayer of the cell membrane to be absorbed.
The focus in this thesis is interactions that may lead to enhanced membrane permeation for peptide drugs.
One approach is the use of helper molecules (permeation enhancers). While the mechanism of many permeation enhancers have been studied to various degrees, little is known about how the presence of the drug affects the mechanisms. In this thesis, we therefore compared the effect of multiple permeation enhancers in the presence of two peptide drugs. We found that permeation enhancer:peptide drug interactions do alter membrane interactions, and that these interactions may further be influenced by bile acids from the fluid in the intestines. This highlights the importance of testing, or at least considering, the properties of the combined permeation enhancer:peptide drug pairs of interest.
We also established a flow cytometry method, by which the above could be tested. Here we used several different peptides that by themselves influenced the lipid bilayer (membrane active peptides). We established that we could investigate multiple properties of the effect of membrane active peptides on lipid membranes concurrently, and in that way provide mechanistic information in a fast manner.
Together, we here present methodologies and insight into the field of permeation enhancement of peptide drugs, which could be usefull for the further mechanistic understanding and development of eg. permeation enhancers.