Rapid generation of protein aerosols and nanoparticles via surface acoustic wave atomization

Abstract

We describe the fabrication of a surface acoustic wave (SAW) atomizer and show its ability to generate monodisperse aerosols and particles for drug delivery applications. In particular, we demonstrate the generation of insulin liquid aerosols for pulmonary delivery and solid protein nanoparticles for transdermal and gastrointestinal delivery routes using 20 MHz SAW devices. Insulin droplets around 3 µm were obtained, matching the optimum range for maximizing absorption in the alveolar region. A new approach is provided to explain these atomized droplet diameters by returning to fundamental physical analysis and considering viscous-capillary and inertial-capillary force balance rather than employing modifications to the Kelvin equation under the assumption of parametric forcing that has been extended to these frequencies in past investigations. In addition, we consider possible mechanisms by which the droplet ejections take place with the aid of high-speed flow visualization. Finally, we show that nanoscale protein particles (50-100 nm in diameter) were obtained through an evaporative process of the initial aerosol, the final size of which could be controlled merely by modifying the initial protein concentration. These results illustrate the feasibility of using SAW as a novel method for rapidly producing particles and droplets with a controlled and narrow size distribution.

Using laser Doppler vibrometry to measure capillary surface waves on fluid-fluid interfaces

“…6,7 Although others have tried controlling the appearance of such waves 8,9 or have considered more complex excitation schemes, 10 the difficulty of accurately measuring the characteristics of the wave while adequately controlling the boundary conditions has limited researchers to work on frequencies of at most a few thousand of hertz. 11 However, there are many practical applications of such capillary waves driven at far higher frequencies-a few to even several hundreds of megahertz-from the production of nanoparticles 12,13 to pulmonary drug delivery 14,15 via atomization, a process believed to occur due to Faraday wave instabilities driven to eventually eject droplets with a size roughly corresponding to one-half the wavelength of the capillary wave. 16 Therefore, by increasing the excitation frequency, f, the capillary wavelength and therefore the droplet size, d, is reduced according to d ϳ f −2/3 .…”

Surface Acoustic Waves: A New Paradigm for Driving Ultrafast Biomicrofluidics

“…This one-step process for nanoparticle synthesis is therefore a straightforward, fast and attractive alternative to the multistep conventional methods for nanoparticle production such as spray drying, nanoprecipitation, emulsion photocross-linking, etc., which are slow and cumbersome. In addition, we have also demonstrated the possibility of generating 100 nm order dimension protein (insulin) nanoparticles as well as 3 µm aerosol droplets for inhalation therapy [21]. Further, it is possible to load protein and other therapeutic molecules into the biodegradable polymer nanoparticle shells produced for controlled release drug delivery [22].…”

Confinement of surface waves at the air-water interface to control aerosol size and dispersity

“…7 Nebulisation has many industrial and medical applications including surface coating, 8 printing of protein microarrays, 9 combustion, 10 spray drying, 11 mass spectrometry, 12,13 nanoparticles synthesis, 14 and drug dispensation through nebulisers [15][16][17] for the treatment of pulmonary diseases. [18][19][20][21] In all cases, obtaining precise control of the droplet size is crucial to achieve a consistent and reproducible delivery of the aerosols.…”