A recent study led by researchers at the University of Toronto sheds new light on a crucial challenge in the field of nucleic acid drug delivery: how to make lipid nanoparticles (LNPs) break down more quickly in the body. This discovery could pave the way for medicines that can be administered more frequently and with fewer side effects.
This research was published in the latest issue of Analytical Chemistry.
LNPs are best-known for their use in mRNA vaccines and are also being explored to deliver a wide range of drugs in the pharmaceutical industry. “We’ve focused a lot on making LNPs that deliver drugs more effectively, but less is understood about what happens to the lipids after they’ve done their job in the cells in the body”, said Professor Omar Khan, the corresponding author of this research and an assistant professor at the Institute of Biomedical Engineering (BME) at the University of Toronto.
In the past it has been difficult to predict how long LNP remains in the body. The researchers aimed to explore this knowledge gap by using an innovative approach – nuclear magnetic resonance (NMR) spectroscopy – which offers a faster, more efficient way to assess lipid biodegradation by enzymes.
NMR spectroscopy works by applying a strong magnetic field to a sample, causing certain atomic nuclei to resonate at specific frequencies. The resulting signals, produced as the nuclei return to their equilibrium state, are analyzed to reveal the chemical structure and environment of molecules in the sample.
“These methods could easily be implemented by other groups with access to NMR facilities”, said Jagriti Natraj, an undergraduate research student and co-author of the study.
The study revealed that the speed at which lipids degrade varies dramatically based on their molecular structure. Some lipids break down quickly by digestive enzymes, while others persist much longer.
“By understanding the relationship between lipid structure and biodegradation, we can design new compounds that break down more rapidly in the body,” explained Julien Couture-Senécal, a PhD student and the study’s lead author. Couture-Senécal and Khan are co-founders of Azane Therapeutics, a biotech startup focused on creating LNPs to improve the delivery of RNA-based drugs.
This research marks a critical step toward improving LNP-based therapies, with potential applications ranging from vaccines to personalized medicines. Faster-degrading LNPs could enable more frequent dosing, better safety, and improved outcomes for patients.