Comparison and validation of a high-throughput lipid nanoparticle production and characterization workflow

Area of Science:

• Nanomedicine
• Biotechnology
• Drug Delivery

Background:

• Lipid nanoparticles (LNPs) carrying RNA are crucial for nanomedicine.
• Optimizing LNP formulations requires modifying payload, lipid composition, and production.
• High-throughput screening necessitates efficient LNP characterization methods.

Purpose of the Study:

• To evaluate high-throughput LNP characterization methods for comparability with traditional techniques.
• To assess the integration of automated systems into LNP formulation workflows.
• To accelerate the development pipeline for RNA therapeutics.

Main Methods:

• Combined a semi-automated microfluidic system with a high-throughput characterization instrument.
• Utilized high-throughput plate reader dynamic light scattering (DLS) for hydrodynamic diameter measurement.
• Performed independent analysis of DLS autocorrelation function data.
• Employed fluorescence-based assays for RNA quantification.

Main Results:

• High-throughput DLS provided comparable hydrodynamic diameter data to conventional methods, with faster analysis times.
• Fluorescence assays demonstrated higher sensitivity for RNA quantification compared to high-throughput DLS.
• The integrated workflow successfully streamlined LNP production and characterization.

Conclusions:

• High-throughput characterization systems can effectively streamline LNP development and formulation screening.
• These automated methods are comparable to traditional techniques and suitable for translational workflows.
• Integrating high-throughput characterization accelerates the development of RNA-based therapeutics.