Continuous production of solid lipid nanoparticles by liquid flow-focusing and gas displacing method in microchannels

Abstract

Abstract The liquid flow-focusing and gas displacing method is developed to produce solid lipid nanoparticles (SLNs) continuously in a microchannel, which has a cross-junction for the focus of lipid and aqueous solutions and a T-junction for the injection of gas bubbles. The liquid flow-focusing was achieved by introducing a lipid solution with a water-miscible organic solvent and an aqueous surfactant solution simultaneously through the two branches of the cross-junction into the main channel, while the gas displacing was accomplished by injecting an inert gas ( N 2 ) through the T-junction at the downstream of the cross-junction into the main flow streams upward to form gas–liquid slug flow. Solid lipid nanoparticles were formed due to the local supersaturation of lipid induced by the diffusion of the solvent from the lipid solution stream into the aqueous phase. The liquid suspension containing solid lipid nanoparticles then passed freely through the microchannel without any blockage by the contribution of gas slug flow. The flow behaviors were observed by a digital inversion microscope system and the hydrodynamics of the liquid flow-focusing streams and the gas slug flow were investigated. Particle size distributions of the solid lipid nanoparticles obtained under various conditions were measured by dynamic light scattering and the particle morphology was examined by transmission electron microscopy. The influences of liquid velocity and lipid concentration under the gas displacing condition on the properties of solid lipid nanoparticles were studied experimentally. The solid lipid nanoparticles with small size (the mean size in the range of 120–200 nm) and narrow particle size distribution (with values of polydispersity index in the range of 0.14–0.19) had been produced by this method. The crucial roles of Taylor bubbles and liquid slugs in the formation of solid lipid nanoparticles were considered and the transfer mechanism of slug flow on the formation and passage of solid lipid nanoparticles in the microchannel were also discussed. Compared with other production methods for SLNs (e.g., hot homogenization, warm microemulsions and supercritical fluid technique), the proposed method in this work is simple and no overcritical operations are needed during the preparing process. Therefore, it can be employed to prepare SLNs with small sizes and a narrow diameter distribution.