High-throughput Screening of Lipid Nanoparticle Formulations
Lipid nanoparticles (LNPs) are increasingly employed to improve delivery efficiency and therapeutic efficacy of nucleic acids. Various formulation parameters can affect the quality attributes of these nanoparticle formulations, but currently there is a lack of systemic screening approaches to address this challenge. We recently developed a high-throughput screening (HTS) workflow for streamline preparation and analytical characterization of LNPs loaded with antisense oligonucleotides (ASOs) in 96-well plates. ASO-loaded LNPs with different formulation compositions were formulated by an automated solvent-injection method using a robotic liquid handler, and assessed for particle size distribution, encapsulation efficiency, and stability. The results from our HTS approach correlated with those from the state-of-the-art scale-up method using a microfluidic formulator, therefore opening up a new avenue for robust formulation development and design of experiment methods, while reducing material usage by 10 folds, improving analytical outputs and accumulation of information by 100 folds.
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2021-08-02
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