Controlled Assembly of Lipid Nanoparticles for RNA Delivery using a Slow Equilibrium Process

Robert Falconer, PhD – Professor, School of Chemical Engineering, University of Adelaide

Poster Presenter(s)

Jessica Boutros, PhD

PhD Candidate
University of Adelaide
Adelaide, South Australia, Australia

Introduction:

Lipid nanoparticles (LNPs) are typically produced by rapid microfluidic mixing of lipid in ethanol with RNA in buffer, a process known as nanoprecipitation. An alternative approach is gradual lipid addition to the RNA. This process has a liquid coacervate intermediate that undergoes spontaneous emulsification to form LNPs. This is thermodynamically controlled, low shear equilibrium process. Initially, it was studied using isothermal titration calorimetry, then translated to a scalable platform for RNA-LNP manufacturing with potential use in the next generation of personalised cancer vaccines.

Learning Objectives:

Explain lipid nanoparticle assembly in terms of a thermodynamically controlled equilibrium process.
Explain how coacervation and spontaneous emulsification drive of lipid nanoparticle formation.
Demonstrate that the equilibrium process is an alternative to microfluidic RNA-LNP manufacturing.