Kelly Zhang of Genentech, USA, gave a keynote presentation on the characterization of lipid nanoparticles (LNPs) at the 51st International Symposium on High-Performance Liquid Phase Separations and Related Technologies (HPLC 2023) held this week. (1).
LNPs have emerged as powerful tools for drug delivery, especially with the success of mRNA-LNP-based COVID-19 vaccines. Analytical characterization of these nanoparticles is of great importance for various aspects such as pharmaceutical design, formulation development, understanding their performance in the body, and ensuring patient safety through quality control.
Although LNP analyzes in various fields such as mRNA, oligonucleotides and small molecules have been studied and widely reported, the literature on the characterization of intact LNPs as final products is lacking. Mr. Zhang explained important quality attributes of LNP pharmaceuticals such as drug encapsulation efficiency, particle size, lipid composition and stability. Mr. Zhang also explored the strengths and weaknesses of current analytical techniques and outlined specific challenges associated with LNP characterization.
According to Zhang, one of the main aspects to consider is sample preparation, or handling of these fragile lipid-aggregated particles. As LNPs are delicate structures, special care must be taken to preserve their integrity during analysis. Furthermore, the complexity of the lipid matrix within LNPs poses challenges for chromatographic separation.
Zhang found that the application of machine learning helps efficiently analyze LNP drugs containing different nucleic acid cargoes such as antisense oligonucleotides (ASOs), guide RNAs (gRNAs) and mRNAs within different lipid matrices. I emphasized that it is possible. In addition, she described a method developed by herself using machine learning for high-throughput quantification of nucleic acid loading on LNPs based on UV detection. Zhang emphasized the need for orthogonal methods to characterize mRNA-LNP products from different angles. She concluded that the characterization and scope of LNPs remain challenging and need to be addressed in further research using separation science and multidimensional analysis.
reference
(1) Zhang, K. Analytical characterization of lipid nanoparticles. Launch location: HPLC 2023, June 18-22, 2023, Düsseldorf, Germany. KN01.
