Long-term storage of lipid-like nanoparticles for mRNA delivery

Lipid-like nanoparticles (LLNs) have been extensively explored for messenger RNA (mRNA) delivery in various biomedical applications. However, the long-term storage of these nanoparticles is still a challenge for their clinical translation. In this study, we investigated a series of conditions for the long-term storage of LLNs with encapsulation of mRNA. We evaluated the stability of LLNs with different concentrations of cryoprotectants (sucrose, trehalose or mannitol) under the conditions of freezing or lyophilization processes. Through in vitro and in vivo mRNA delivery studies, we identified the optimal storage condition, and found that the addition with 5% (w/v) sucrose or trehalose to LLNs could remain their mRNA delivery efficiency for at least three months in the liquid nitrogen storage condition. [Display omitted] •The stability of lipid-like nanoparticles (LLNs) are evaluated under aqueous, freezing, or lyophilization conditions.•Effects of cryoprotectants on LLNs stability are investigated with the freezing and lyophilization processes.•5% (w/v) sucrose or trehalose LLNs stored in liquid nitrogen remain mRNA delivery efficiency for over three months.