International journal of pharmaceuticsSep 12, 2024

Improving protective agents to make DNA-loaded lipid nanoparticles more stable and effective for gene delivery

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 8, 2026

Abstract

Trehalose maintained lipid nanoparticle stability for up to 2 years after freeze-drying.

Substituting mRNA with pDNA in lipid nanoparticles may enhance stability and efficacy.
Cryoprotectants could mitigate destabilization during freeze-drying of pDNA-loaded lipid nanoparticles.
Different concentrations of cryoprotectants were evaluated for their impact on the physicochemical properties and transfection efficiency of lipid nanoparticles.
Biological efficacy was confirmed post-storage under various conditions.
Optimized cryoprotectant concentrations sustain lipid nanoparticle stability during freeze-drying and prolonged storage.

Simplified

Advances in gene therapy, exemplified by mRNA vaccines against COVID-19, highlight the importance of lipid nanoparticles (LNPs) for nucleic acid delivery despite challenging storage conditions. Substituting mRNA with pDNA in LNPs may enhance stability and efficacy, yet maintaining LNP stability poses challenges, particularly during freeze-drying. Cryoprotectants offer potential to mitigate destabilization, improving LNP properties and in vivo performance. Here, we evaluated the effects of different concentrations of various cryoprotectants on the freeze-drying process of pDNA-loaded LNPs, assessing their physicochemical characteristics and transfection efficiency. Stability was examined under various storage conditions, confirming biological efficacy post-storage. Our results highlight the role of cryoprotectants in optimizing freeze-drying for the extended shelf life of nucleic acid-loaded LNPs. Trehalose emerged as an efficient cryoprotectant, maintaining LNP stability after the freeze-drying process for up to 2 years, with diameters and transfection efficiency comparable to fresh formulations. These findings demonstrate the optimized concentration of cryoprotectants to sustain LNP stability despite freeze-drying and prolonged storage, providing valuable insights for nucleic acid-based therapies.

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Competing interests

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Improving protective agents to make DNA-loaded lipid nanoparticles more stable and effective for gene delivery

Abstract

Full Text

Funding

Competing interests

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