Flash nanoprecipitation enables regulated formulation of soybean protein isolate nanoparticles

Soy protein isolate (SPI) is perspective building block for fabrication of cargo-loaded nanoparticles (NPs) based on different formulation strategies. Particularly, precipitation demonstrates an easy and widespread fabrication approach, whereas most of the reported precipitation methods rely on spontaneous aggregation of SPI which typically suffers from the poor control on particle size and limited drug loading capacity. Herein, we reported a flash nanoprecipitation (FNP) method for regulated formulation of lutein-loaded SPI NPs. Specifically, solvent streams containing SPI and lutein are mixed with anti-solvent streams in a multi-inlet vortex mixer. Different control factors including lutein/SPI mass ratio and flow rate are investigated, and the obtained lutein-loaded SPI NPs show regulated particle size (80–122 nm), narrow size distribution (PDI ∼ 0.2), enhanced drug loading content (20%), high stability and improved bioaccessibility of lutein up to 94%. All these desirable properties are related to the kinetically trapped state of NPs due to the rapid mixing of FNP, which shall be hardly achieved with conventional precipitation approaches. Along with other intrinsic features such as fast mixing and continuous production, FNP possesses distinctive advantages for efficient fabrication of drug-loaded SPI NPs with regulated size and properties which are favorable for diverse delivery applications.