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The development of functional lipid nanoparticles (LNPs) is one of the major challenges in the field of drug delivery systems (DDS). Recently, LNP-based RNA delivery systems, namely, RNA-loaded LNPs have attracted attention for RNA therapy.In particular, mRNA-loaded LNP vaccines were approved to prevent COVID-19, thereby leading to the paradigm shift toward the development of next-generation nanomedicines. For the LNP-based nanomedicines, the LNP size is a significant factor in controlling the LNP biodistribution and LNP performance. Therefore, a precise LNP size control technique is indispensable for the LNP production process. Here, we report a protocol for size controlled LNP production using a microfluidic device, named iLiNP. siRNA loaded LNPs are also produced using the iLiNP device and evaluated by in vitro experiment. Representative results are shown for the LNP size, including siRNA-loaded LNPs, Z-potential, siRNA encapsulation efficiency, cytotoxicity, and target gene silencing activity.

The function of liposomal drugs and cosmetics is not only controlled by the lipid composition/formulation, but also by the liposome size and internal structure/properties (uni- and multi-lamellae) and membrane rigid/fluidic...

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.