Production of protein nanoparticles by electrospray drying

Abstract

The feasibility of producing relatively monodisperse and biologically active insulin particles by electrospray drying is demonstrated. The process entails dissolving dry insulin in an acidic ethanol–water solution. The solution is then electrosprayed and, after solvent evaporation, dry residues can be collected on suitable deposition substrates. Particles were sized visually, using a scanning electron microscope (SEM), and aerodynamically, using an inertial impactor. When electrosprays of nearly saturated solutions were operated in the stable cone-jet mode, impactor data showed that the particle average aerodynamic diameter ranged from about 88 to 110 nm in diameter and the distributions were quasi-monodisperse with relative standard deviation estimated at approximately 10%. SEM obsevations for the same conditions showed average particle dimensions ranging from 98 to 117 nm, with predominantly doughnut shapes. Smaller particles can be generated by decreasing the insulin concentration and/or by spraying smaller liquid flow rates. Although the maximum production rate for monodisperse insulin nanoparticles from a single cone-jet is low, at about 0.23 mg h-1 overall production can be increased by multiplexing the device with microfabrication techniques. Increasing production rate from a single cone-jet by at least one order of magnitude can be achieved also by increasing the liquid flow rate. The resulting particles have larger sizes, on the order of 600 nm, but particle monodispersity is compromised and particle morphology is drastically modified, probably as a consequence of a different electrospray operating mode. The biological activity of the electrospray-processed insulin samples was confirmed by comparing binding properties on insulin receptors against a control sample.