Understanding the enhanced mRNA functional delivery of lipid nanoparticles formulated using a high-throughput platform
Biopharmaceutical company, AstraZeneca, recently developed an automated technique to generate lipid nanoparticles for mRNA delivery and used neutron scattering to investigate how it compared to standard production methods.
The challenge
Lipid nanoparticle (LNP) encapsulation is one of the most successful non-viral delivery technologies to shield mRNA from degradation. To accelerate the study of LNPs, a team from AstraZeneca developed an automated high-throughput platform to generate and screen LNPs for mRNA delivery. The team wanted to evaluate the mechanistic and physiochemical properties of LNPs prepared using the automated process, to understand their enhanced mRNA functional delivery compared to those produced by a standard microfluidic mixing platform.
The experiment
The AstraZeneca team exploited the complementarity of small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) to compare the internal structure of LNPs generated using the new automated process versus those generated by the standard process.
The results
The studies revealed that LNPs produced using the automated system were larger, had a higher mRNA loading, a more hydrophobic surface, and more hemolytic and beneficial cellular uptake pathways. As a result, LNPs made using the new automated platform were 4.5 times more effective than those made via the standard protocol.
Crucially, the findings have provided valuable insight to accelerate research and development of mRNA therapeutics.
"We deeply appreciate the support from ISIS facility and scientists for the neutron beam time and the valuable knowledge which help us unveil the internal and surface property of the mRNA LNP nanoparticles,"
Lili Cui
Senior Scientist Formulation Advanced Drug Delivery, AstraZeneca
