The preparation of lipid-based nanoparticles (LNPs) using microfluidic devices offers significant advantages, such as precise size control and easy scale-up, in a continuous manufacturing system. However, improvements in this preparation method are needed to enhance LNP productivity to meet commercial, such as clinical and consumer, demands. Feeding a highly concentrated lipid solution into microfluidic devices to obtain a high concentration of LNPs is one of the ways to boost productivity. However, this has not been investigated in detail because a high concentration of lipids in ethanol makes it difficult to control the size and dispersity of LNPs. We previously developed iLiNP, a microfluidic device with simple baffle mixer structures, which can achieve rapid ethanol dilution. The applicability of iLiNP for producing LNPs by feeding a highly concentrated lipid solution has not been investigated. Herein, we demonstrate the preparation of monodispersed LNPs using a highly concentrated lipid solution. We compare the performance of iLiNP with those of three commercially available microfluidic devices. The area of the aqueous−ethanol interface and the dilution rate of ethanol significantly affects the size controllability and dispersity of LNPs at high lipid concentrations. Compared with other microfluidic devices, iLiNP could produce smaller and more concentrated (particles/mL) LNPs. We show that by controlling the LNP size using microfluidic devices, especially iLiNP, it is possible to feed highly concentrated lipid solutions. This feature of iLiNP could be a time-and cost-saving option for the mass production of LNPs for application in nanomedicine and cosmetics.

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.