Generation of Monodisperse Protein Nanoparticles by Electrospray Drying

The feasibility of producing relatively monodisperse and biologically active protein particles by electrospray drying is demonstrated. The process entails dissolving dry powder in an electrosprayable solution. The solution is then dispersed and, after solvent evaporation, dry residues can be collected on suitable deposition substrates. The process was demonstrated in the case of insulin. 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 observations 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. The biological activity of the electrospray-processed insulin samples was confirmed by comparing binding properties on insulin receptors against a control sample. Although the maximum production rate for monodisperse insulin nanoparticles from a single cone-jet is low, at about 0.23 mg/hour, overall production can be increased by multiplexing the device with microfabrication techniques.