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Covid vaccine based on lipid nanoparticles (LNP) have been the success story of the covid

pandemic. Our group has been working on the long-term stability of liquid formulation of
mRNA like LNP particles in collaboration with the industry. However, their rapid approval
was made at the expense of an optimisation of the formulation, especially its excipients.
When selecting excipients for a formulation, researchers should remember the product may
need to be stored at sub-zero temperatures and excipients affect that milieu.

The choice of the buffering system and osmolyte is important as the pH may change upon
freezing, as has been shown for sodium phosphate buffered systems; whilst histidine buffers
are more ‘pH-resistant’ upon freezing (Kolhe et al., 2010). Other excipients such as sodium
chloride, antioxidants, metal chelators can be added but it remains unclear how much they
improve the stability of mRNA-LNP formulations during storage (Wayment-Steele, 2020).

Here, in this project, we seek to increase scientific knowledge and understanding of the role
of excipients on the stability of LNPs upon storage. LNPs will be produced and formulated
in presence of different excipients and buffers, their physicochemical properties
characterised, their stability over time and their ability to deliver their payload will be
characterised. Several techniques will be used including microfluidics, light scattering, zeta
potential, electron microscopy, confocal microscopy, cell culture or electrophoresis.

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