Abstract

Fabrication of Engineered Lipid Nanoparticles Using Microfluidic Devices

Manabu Tokeshi, Professor, Hokkaido University

Recently, the production of lipid nanoparticles (LNPs) using microfluidic devices has attracted much attention. Microfluidic devices provide many advantages for drug-loaded LNP production, including precise LNP size controllability, high reproducibility, high-throughput optimization of LNP formulation, and continuous LNP-production processes. Various microfluidic devices have been developed and used to produce LNPs encapsulating RNA, DNA, ribonucleoproteins (RNPs), drugs, and others. In fact, microfluidic devices are also being used in the development of Onpattro®, which was approved by the FDA in 2018 as an RNA interference therapeutic drug. Recently, we developed a microfluidic device named iLiNP® (invasive lipid nanoparticle production) device for LNP production based on computational fluid dynamics and LNP formation mechanism. It enabled the LNP size tuning at 10 nm intervals in the size range from 20 to 100 nm. Using this device, we have not only developed pharmaceutical applications by producing LNPs encapsulating nucleic acids and drugs, but also devices integrating the post-processing of LNP production and devices for mass production. Moreover, very recently, we have found that iLiNP devices are also highly suitable for the fabrication of functional (engineered) lipid nanoparticles such as artificial exosomes and virus-like particles. In this lecture I will present these results.