Continuous synthesis of stable ferrocene nanoparticles using a self-aligned coaxial turbulent jet mixer

Abstract

Ferrocene nanoparticles possess an outstanding characteristic as a drug delivery carrier, in being able to trigger on-demand release of drugs in a specific condition with reactive oxygen species (ROS). However, due to the limitation of the conventional bulk nanoprecipitation method, uniform and highly stable nanoparticles have still been difficult to develop. In this study, we developed device-mediated ferrocene nanoparticles (D-FNPs) with highly controlled uniform size and long-term stability through a flash nanoprecipitation method using a self-aligned coaxial turbulent jet mixer. The self-aligned coaxial turbulent jet mixer could be easily assembled using commercial tube fittings, which enabled the coaxial self-alignment of fluidic parts. In addition, by utilizing diaphragm pumps and pulsation dampers for the control of fluid flow, the coaxial turbulent jet mixer could be operated in a fully continuous manner. Thus, the D-FNPs could be prepared in a continuous manner with a high production rate of 633 mg/min. The D-FNPs were highly stable in aqueous media for 3 months. In addition, after lyophilization without any cryoprotectants, the D-FNPs exhibited stable dispersion in aqueous solution. Importantly, the D-FNPs maintained their original outstanding ROS-responsive characteristics, while showing no cytotoxicity.