Microfluidic Platform Enabling Efficient On-Device Preparation of Lipid Nanoparticles for Formulation Screening

Abstract

To obtain an optimal lipid nanoparticle (LNP) formulation, it is necessary to consider various formulation and process parameters related to the quality of LNPs and efficacy of active ingredients. Microfluidic technology has become the most widely used method of LNP production. Although this technology facilitates size control and improves production output, there is a need for a screening platform to optimize LNP formulations. This study describes the development and application of a microfluidic platform equipped with multiple microchannels that allows the tuning of LNP compositions by adjusting the flow rate of the ethanol phases. We found that the LNPs prepared using our platform were almost equivalent in size to those prepared by the conventional off-device mixing process. We prepared siRNA-loaded LNPs with different cationic lipid ratios and amounts of PEGylated lipid modifications and confirmed the corresponding variation in particle size and polydispersity. siRNA-loaded LNPs with different amounts of PEGylated lipid modification were evaluated in vitro, and the optimal amount of PEGylated lipid with high siRNA knockdown activity was determined. The microfluidic platform has the potential to save time and effort in LNP-formulation screening as well as reduce the waste of expensive RNAs and other bioactive ingredients. We anticipate that this microfluidic platform will promote the rapid formulation of clinically effective LNPs.

Controlling lamellarity and physicochemical properties of liposomes prepared using a microfluidic device

“…1 Lb-NPs have the great advantages of high biocompatibility and biodegradability. 5 Based on these characteristics, LNPs have been utilized for the vaccines against COVID-19 1,6-8 and liposomes are widely used in pharmaceutical products such as Doxil, 1,6,9 AmBisome, 6,10 and cosmetic products. 11 The most basic Lb-NPs are liposomes, which are enclosed vesicles consisting of one or more lipid bilayers.…”