An acoustic microscopy technique to assess particle size and distribution following needle-free injection

Needle-free injection is a novel technique for transdermal drug and vaccine delivery, the efficacy of which depends on the number density and mean penetration depth of particles beneath the skin. To date, these parameters have been assessed optically, which is time-consuming and unsuitable for use in vivo. The present work describes the development of a scanning acoustic microscopy technique to map and size particle distributions following injection. Drug particles were modeled using a polydisperse distribution of polystyrene spheres, mean diameter 30.0 mum, and standard deviation 16.7 mum, injected into agar-based tissue-mimicking material, and later, as polydisperse stainless steel spheres, mean diameter 46.0 mum, and standard deviation 13.0 mum, injected both into agar and into porcine skin. A focused broadband immersion transducer (10-75 MHz), driven in pulse-echo mode, was scanned over the surface of the injected samples. Recorded echo signals were post-processed to deduce particle penetration depth (30-300 mum). Furthermore, post-injection size distribution of the spheres was calculated using a novel, automated spectral analysis technique. Experimental results were validated optically and found to predict penetration depth and particle size accurately. The availability of simultaneous particle penetration depth and particle size information makes it possible for the first time to optimize particle design for specific drug delivery applications.