Molecular pharmaceuticsFeb 6, 2026

How Silicone Oil and Storage Conditions Affect the Physical and Functional Stability of mRNA Nanoparticles, Highlighting the Importance of mRNA Structure

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Silicone oil and storage conditions affected mRNA-LNP stability in ways that depended on the RNA cargo.

Evidence

This formulation stability experiment tested Poly A- and eGFP-mRNA LNPs with silicone oil at 4 C, 25 C, and under light exposure, measuring particle properties, encapsulation, mRNA integrity, and transfection.

Caveat

The findings come from model RNAs and stress-storage assays, with mRNA secondary structure proposed as a likely explanation rather than proven across therapeutic mRNAs.

Simplified

Lipid nanoparticles (LNPs) have emerged as a leading platform for mRNA delivery; however, their compatibility with prefilled syringes (PFS) containing silicone oil (SO) as a lubricant remains unexplored. This study investigated the effects of SO on the physicochemical stability and biological activity of mRNA-LNPs under various storage conditions (4 °C, 25 °C, and light exposure). Using polyadenylic acid (Poly A) and enhanced green fluorescent protein-encoding mRNA (eGFP-mRNA) as models, we evaluated particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), and transfection efficacy. The results showed that Poly A-LNPs exhibited significant particle size increases and PDI changes at 25 °C with SO, whereas eGFP-LNPs maintained stability under the same conditions, probably because of the mRNA secondary structure enhancing colloidal stability. At 4 °C, both formulations remained stable for 12 weeks, but long-term storage led to a gradual EE reduction. Under light exposure, eGFP-LNPs retained a high EE but suffered severe mRNA degradation, resulting in a near-complete loss of transfection activity. Notably, SO partially mitigated light-induced damage, improving transfection efficiency by up to 6-fold in 100 ppm (ppm) SO-spiked samples. These findings reveal mRNA-dependent LNP-SO interactions and underscore the necessity of evaluating both the physicochemical and functional stability of PFS-based mRNA-LNP formulations.