Continuous and large-scale fabrication of lecithin stabilized nanoparticles with predictable size and stability using flash nano-precipitation

Abstract

Continuous and large-scale production of phospholipids stabilized emulsions and nanoparticles with controllable particle size and stability has always been a challenge. Here, we use flash nano-precipitation (FNP) to produce lecithin stabilized α-tocopheryl acetate (Vitamin E-acetate) particles at a production rate much higher than conventional batch mixing and thin-film hydration. The FNP produces particles with more homogeneous lecithin coverage comparing to conventional slow mixing. As determined by dynamic/electrophoretic light scattering, transmission electron microscope (TEM) and Quartz Crystal Microbalance with Dissipation (QCM-D), particles with low percent core are covered by thick multiple lecithin layers and aggregate easily with the coalescence of lecithin shell; particles with medium percent core content are covered with a thin layer of lecithin, which provides a high enough ζ-potential to stabilize the particle; for particles with percent core higher than 95%, the large spacing between lecithin molecules result in Ostwald ripening and aggregation. With a given composition, the particle size and stability could both be precisely predicted using the Smoluchowski's diffusion limited particle growth model and the Derjaguin-Landau, Verwey-Overbeek (DLVO) theory. This work demonstrates that the compositions affect the adsorption of phospholipid molecules at the particle surface, which further control particle size and stability.