Objective: To explore the feasibility of lyophilization of mRNA vaccine

LNP (Lipid nanoparticle) is more complex than lyophilization. LNP is a nanostructured particle made of a specific type of lipid in a certain proportion and assembled by a clear process. During LNP preparation, physicochemical parameters such as particle size, dispersion and appropriate effective drug encapsulation rate are very important because they directly affect the biological properties of LNP. These parameters must be preserved during the lyophilization process and subsequent storage.

In order to ensure the preservation of LNP, it is critical to select the appropriate lyophilized buffer, cycle process parameters and temperature. These factors can help maintain the stability and activity of LNP, thus ensuring that it does not change during storage. Therefore, when preparing and preserving LNP, the selection and control of these factors need to be carefully considered to ensure the stability of its quality and effect.

Relevant studies have shown that LNPs containing small interference (si) RNA or mRNA can be successfully freeze-dried, but other researchers have found that siRNA-LNPs can be freeze-dried, but the efficacy (gene silencing effect in cell culture) is significantly reduced after resolution with water.

Two recent studies have shown that the mRNA-LNP platform can be freeze-dried. Zhao et al. studied lyophilized mrNA-LNP encoding firefly fluorescein, and confirmed that the redissolved product maintained mRNA expression efficiency through bioluminescence imaging studies in mice. Hong et al. developed a freeze-dried SARS-CoV-2 mRNA-LNP vaccine formulation and showed that the vaccine can induce a strong immune response in mice.