A pH of 4 in the mRNA aqueous solution optimized encapsulation efficiency and cellular expression, while 300 mM sucrose was essential for maintaining freeze-thaw stability of mRNA/LNPs.
Optimizing the pH of mRNA aqueous solutions to 4 and using 300 mM sucrose significantly improves the encapsulation efficiency, cellular expression, and freeze-thaw stability of SM102-based mRNA/LNPs.
Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, enabling significant advances in mRNA-based therapeutics. While extensive research has focused on lipid composition, the impact of preparation solutions on LNP performance remains underexplored. This study systematically investigated the effects of pH, salt type, and concentration across key preparation solutions-mRNA aqueous, dilution, exchange, and storage solutions-on the physicochemical properties, stability, and expression efficiency of SM102-based mRNA/LNPs. Findings revealed that the pH of the mRNA aqueous solution was critical, with a pH of 4 optimizing encapsulation efficiency (EE) and cellular expression. The exchange solution's pH significantly influenced biodistribution, particularly liver-specific expression following intravenous and intramuscular administration. Sucrose was identified as essential for freeze-thaw stability, with a 300 mM concentration minimizing aggregation and mRNA leakage. Furthermore, preparation solutions were shown to influence the structural integrity of LNPs, impacting their in vivo and in vitro performance. These insights highlight the importance of preparation conditions in optimizing LNP formulations for clinical applications, offering a foundation for enhanced therapeutic design and delivery.
Tang et al. (Wed,) reported a other. Optimized LNP preparation solutions (pH 4 mRNA solution, 300 mM sucrose) vs. Alternative preparation solutions was evaluated on Physicochemical properties and luciferase expression. A pH of 4 in the mRNA aqueous solution optimized encapsulation efficiency and cellular expression, while 300 mM sucrose was essential for maintaining freeze-thaw stability of mRNA/LNPs.