Journal
JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
Volume 127, Issue 4, Pages 2252-2261Publisher
ACOUSTICAL SOC AMER AMER INST PHYSICS
DOI: 10.1121/1.3314252
Keywords
acoustic microscopy; acoustic signal processing; biomedical measurement; biomedical transducers; biomedical ultrasonics; drugs; echo; particle size measurement; polymers; size measurement; skin; spectral analysis; stainless steel; ultrasonic measurement; ultrasonic transducers
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Funding
- U.K.'s Engineering and Physical Sciences Research Council
- Particle Therapeutics Ltd.
- Royal Society
- CenSSIS
- National Science Foundation [EEC-9986821]
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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 mu m, and standard deviation 16.7 mu m, injected into agar-based tissue-mimicking material, and later, as polydisperse stainless steel spheres, mean diameter 46.0 mu m, and standard deviation 13.0 mu m, 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 mu m). 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.
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