PRODUCTION OF PROTEIN NANOPARTICLES BY ELECTROSPRAY DRYING

The feasibility of producing relatively monodisperse and biologically active insulin particles by electrospray drying is demonstrated. The p rocess entails dissolving dry insulin in an acidic ethanol-water solut ion. The solution is then electrosprayed and, after solvent evaporatio n, dry residues can be collected on suitable deposition substrates. Pa rticles 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 mo de, impactor data showed that the particle average aerodynamic diamete r ranged from about 88 to 110 nm in diameter and the distributions wer e quasi-monodisperse with relative standard deviation estimated at app roximately 10%. SEM observations for the same conditions showed averag e particle dimensions ranging from 98 to 117 nm, with predominantly do ughnut shapes. Smaller particles can be generated by decreasing the in sulin concentration and/or by spraying smaller liquid flow rates. Alth ough the maximum production rate for monodisperse insulin nanoparticle s from a single cone-jet is low, at about 0.23 mg h(-1) overall produc tion can be increased by multiplexing the device with microfabrication techniques. Increasing production rate from a single cone-jet by at l east one order of magnitude can be achieved also by increasing the liq uid flow rate. The resulting particles have larger sizes, on the order of 600 nm, but particle monodispersity is compromised and particle mo rphology is drastically modified, probably as a consequence of a diffe rent electrospray operating mode. The biological activity of the elect rospray-processed insulin samples was confirmed by comparing binding p roperties on insulin receptors against a control sample. (C) 1998 Else vier Science Ltd. All rights reserved.