Lipid-based drug delivery systems - stability, protein interaction and leakage in blood plasma with varying composition

Delivery of pharmaceutical substances to patients requires formulations that protects the active substance and ensures desired release in the body. An approach in parenteral delivery is nanoparticles where lipids form structures to embed the active substance.

Hot examples are some of the approved vaccines against the COIVD-19 pandemic where RNA is encapsulated in lipid nanoparticles.

Although being promising vehicles for delivery for decades, relatively few approved formulations exist as there are crucial challenges that need to be overcome.

Some central issues: rapid clearance of particles from the blood stream significantly reducing efficacy, lack of structural stability/integrity and unwanted leakage of the active substance from the particles.

Major steps have been taken to address these issues, but much of the analysis is only performed in the pharmaceutical formulation. Little is known of the fate of the particles when they come in contact with components of the blood stream. We aim to address these issues by studying the interaction and behaviour of lipid nanoparticles in blood plasma.

The research will establish how blood protein-lipid nanoparticle interaction affects blood clearance/stability/leakage.

The composition of blood plasma will also be altered to mimic compositions related to age, gender and conditions such as propensity for cardiovascular disease and thrombosis. This will reveal aspects of how individual variation may affect the pharmaceutical efficacy.