Using scattering methods to characterise the structure of lipid nanoparticles for biomolecule encapsulation

DRA lecture held by Postdoctoral Researcher Jennifer Gilbert, Chalmers University of Technology Göteborg, Sweden

The use of lipid nanoparticles (LNPs) and vesicles for drug delivery, especially for nucleic acid-based drugs, is a rapidly growing field. LNPs can have a range of different structures depending on their lipid composition, cargo and formulation conditions. The internal structure of LNPs varies from highly ordered, such as the periodic water channel networks in cubosomes, to more disordered structures, such as the LNP based vaccines against SARS-CoV-2. Although it has been shown that LNPs with different structures have different in vitro efficacy, rational design of LNP and vesicle formulations remains challenging due to limited understanding of structure-function relationships, the effect of the biological environment on structure and interactions with the cellular environment (e.g. membranes) in biological samples. An additional challenge lies in the structural heterogeneity often present in LNP formulations, especially as these sub-populations are difficult to quantify using traditional ensemble methods. Using a combination of neutron and x-ray scattering methods, we have characterised the effect of different factors on the structure of LNP formulations, including the importance of specific lipid-cargo interactions and the effect of the buffer during and post-formulation. Two examples will be presented here: 1) lipid sponge phase with proteins relevant to the food industry; and 2) Onpattro formulation LNPs with model nucleic acids. Finally, I will introduce more recent work exploring methods to detect and quantify the presence of vesicle sub-populations in a range of LNP formulations, using a combination of ensemble and single particle methods.

The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Tenure Track Assistant Professor Federica Sebastiani, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen.

The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.