Rapid generation of protein aerosols and nanoparticles via surface acoustic waveatomization

Abstract

We describe the fabrication of a surface acoustic wave (SAW) atomizer and showits ability to generate monodisperse aerosols and particles for drug deliveryapplications. In particular, we demonstrate the generation of insulin liquid aerosolsfor pulmonary delivery and solid protein nanoparticles for transdermal andgastrointestinal delivery routes using 20 MHz SAW devices. Insulin droplets around3 µm were obtained, matching the optimum range for maximizing absorption in the alveolarregion. A new approach is provided to explain these atomized droplet diameters byreturning to fundamental physical analysis and considering viscous-capillary andinertial-capillary force balance rather than employing modifications to the Kelvin equationunder the assumption of parametric forcing that has been extended to these frequenciesin past investigations. In addition, we consider possible mechanisms by whichthe droplet ejections take place with the aid of high-speed flow visualization.Finally, we show that nanoscale protein particles (50–100 nm in diameter) wereobtained through an evaporative process of the initial aerosol, the final size ofwhich could be controlled merely by modifying the initial protein concentration.These results illustrate the feasibility of using SAW as a novel method for rapidlyproducing particles and droplets with a controlled and narrow size distribution.