Boosting LNP Performance: Higher Concentrations of Lipid Mixtures Improve In Vivo Gene Expression and Storage...

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery

Background:

• Lipid nanoparticles (LNPs) are critical for nucleic acid therapeutics.
• Formulation efficiency directly impacts therapeutic success.
• Optimizing LNP formulation is essential for drug development.

Purpose of the Study:

• Investigate the effect of lipid and payload concentrations on LNP properties.
• Evaluate LNP performance at elevated starting material concentrations.
• Assess the impact of buffer composition and formulation intensification.

Main Methods:

• Utilized confined jet-impingement mixing for LNP formulation.
• Analyzed LNP particle size, polydispersity index, and morphology (CryoTEM).
• Conducted in vivo studies in mice to assess gene expression and biodistribution.

Main Results:

• Desired LNP properties maintained at 70 mg/mL lipid concentration.
• Particle size and polydispersity index remained stable.
• Higher concentrations yielded more uniform LNPs with solid cores.
• Buffer composition influenced LNP characteristics and stability.
• In vivo studies showed enhanced gene expression with higher concentrations and Tris-sucrose buffer.

Conclusions:

• Intensified mixing enables higher starting material concentrations for LNP formulations.
• Elevated concentrations improve mRNA-LNP biological performance and stability.
• This approach enhances scalability and throughput for LNP production.