Microfluidic Device-Enabled Mass Production of Lipid-Based Nanoparticles for Applications in Nanomedicine and Cosmetics

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.