In the realm of mRNA therapeutics, lipid nanoparticles (LNPs) have emerged as a groundbreaking delivery system, most notably with the success of COVID-19 vaccines. However, the stability of these LNPs has posed significant challenges, limiting their widespread application. A recent study published in *MedComm – Biomaterials and Applications* (which translates to *Materials and Applications* in English) sheds new light on the stability of LNPs, focusing on the role of ionizable lipids. The research, led by Jie Wang from the School of Life Science at the Beijing Institute of Technology, could have profound implications for the future of mRNA-based treatments and their commercial viability.
The study investigated the thermostability of two ionizable lipids: an in-house developed lipid (A1-D1-5) and SM-102, which is used in FDA-approved mRNA therapeutics. The researchers assessed the stability of LNPs composed of these lipids under various storage conditions. Their findings revealed that traditional indicators such as size and polydispersity index (PDI), measured by dynamic light scattering (DLS), did not accurately reflect the stability of LNPs. Even after 44 days of storage at 4°C, these indicators showed little change, yet the mRNA activity sharply declined within just 14 days of preparation.
“This discrepancy highlights the need for more sophisticated methods to evaluate LNP stability,” said Jie Wang, the lead author of the study. “Our findings suggest that the thermostability of ionizable lipids plays a crucial role in maintaining mRNA activity over time.”
One of the most significant discoveries was that A1-D1-5 demonstrated greater thermostability compared to SM-102, leading to a slower decrease in mRNA activity. The researchers also found that replacing ester bonds with amide bonds in the lipid structure significantly improved thermostability. This insight could pave the way for the development of more stable and effective LNP formulations.
The implications of this research extend beyond the laboratory. For the energy sector, which is increasingly exploring the use of mRNA-based technologies for various applications, the stability of LNPs is a critical factor. Enhanced stability could lead to more efficient and cost-effective production, storage, and distribution of mRNA therapeutics, ultimately benefiting both patients and the industry.
As the field of mRNA therapeutics continues to evolve, the findings from this study provide valuable insights into optimizing and evaluating the stability of LNP formulations. By understanding the fundamental rules behind LNP stability, researchers can develop more robust and reliable delivery systems, opening up new possibilities for the future of medicine.
In the words of Jie Wang, “This research is just the beginning. There is still much to learn about the stability of LNPs, but our findings provide a solid foundation for future advancements in the field.”