The effect of cryoprotectants and storage conditions on the transfection efficiency, stability and safety of lipid-based nanoparticles for mRNA and DNA delivery

Kostas Kafetzis, Natalia Papalamprou, Elisha Mcnulty, Kai Thong, Yusuke Sato, Aleksandr Mironov, Atul Purohit, PHILIP WELSBY, Hideyoshi Harashima, Cynthia Yu-Wai-Man, ARISTIDES TAGALAKIS*

*Corresponding author for this work

Research output: Contribution to journalArticle (journal)peer-review

6 Citations (Scopus)
1 Downloads (Pure)

Abstract

Lipid-based nanoparticles have recently shown great promise, establishing themselves as the gold standard in delivering novel RNA therapeutics. However, research on the effects of storage on their efficacy, safety and stability is still lacking. Herein, the impact of storage temperature on two types of lipid-based nanocarriers, lipid nanoparticles (LNPs) and receptor-targeted nanoparticles (RTNs), loaded with either DNA or messenger (RNA) is explored, and the effects of different cryoprotectants on the stability and efficacy of the formulations are investigated. The medium-term stability of the nanoparticles was evaluated by monitoring their physicochemical characteristics, entrapment and transfection efficiency, every 2 weeks over one month. It is demonstrated that the use of cryoprotectants protects nanoparticles against loss of function and degradation in all storage conditions. Moreover, it is shown that the addition of sucrose enables all nanoparticles to remain stable and maintain their efficacy for up to a month when stored at -80°C, regardless of cargo or type of nanoparticle. DNA-loaded nanoparticles also remained stable in a wider variety of storage conditions than mRNA-loaded ones. Importantly, these novel LNPs showed increased GFP expression that could signify their future use in gene therapies, beyond the established role of LNPs in RNA therapeutics.
Original languageEnglish
JournalAdvanced healthcare materials
Early online date14 Mar 2023
DOIs
Publication statusPublished - 2023

Keywords

  • lipid nanoparticle
  • DNA
  • mRNA
  • cryoprotectant
  • stability

Research Institutes

  • Health Research Institute

Research Centres

  • Data Science STEM Research Centre
  • Cardio-Respiratory Research Centre

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