Projects per year
Abstract
Lipid nanoparticles (LNPs), most commonly recognised for their role in COVID-19 mRNA vaccines, are important delivery vehicles for nucleic acid (mRNA, siRNA) therapies. The physicochemical attributes, such as size, nucleic acid encapsulation and electric charge, may have a significant impact on the efficacy of these medicines. In this study, adjustments to aqueous to lipid phase ratios were assessed for their impact on LNP size and other critical quality attributes (CQAs). It was observed that minor adjustments of aqueous-to-organic lipid phase ratios can be used to precisely control the size of ALC-0315-formulated LNPs. This was then used to evaluate the impact of phase ratio and corresponding size ranges on the in vitro and in vivo expression of these LNPs. In HEK293 cells, larger LNPs led to higher expression of the mRNA cargo within the LNPs, with a linear correlation between size and expression. In THP-1 cells this preference for larger LNPs was observed up to 120 d.nm after which there was a fall in expression. In BALB/c mice, however, LNPs at the lowest phase ratio tested, >120 d.nm, showed reduced expression compared to those of range 60–120 d.nm, within which there was no significant difference between sizes. These results suggest a robustness of LNP expression up to 120 d.nm, larger than those
Original language | English |
---|---|
Pages (from-to) | 841-853 |
Number of pages | 13 |
Journal | RSC Pharmaceutics |
Volume | 1 |
Issue number | 4 |
Early online date | 23 Sept 2024 |
DOIs | |
Publication status | E-pub ahead of print - 23 Sept 2024 |
Keywords
- Lipid nanoparticles (LNPs)
- lipid phase ratios
- medicines
Fingerprint
Dive into the research topics of 'Tailoring lipid nanoparticle dimensions through manufacturing processes'. Together they form a unique fingerprint.Projects
- 1 Active
-
Impact on formulation composition on efficacy and properties of LNPs for delivery
Croda Europe Limited, BBSRC (Biotech & Biological Sciences Research Council)
1/09/22 → 31/08/26
Project: Research - Studentship