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An investigation on the use of micro-ultrasonic-transducers for anticancer drugs cytotoxicity enhancement

University of British Columbia

Prototype ultrasonic transducers with resonance frequencies at 4 and lMHz were constructed using lead zirconate titanate (PZT) ceramics. Their output ultrasonic powers were measured using an electronic ultrasound power meter. The power coefficients of the 4 and 1 MHz transducers were found to be 1.98 and 1.85 respectively, close to the theoretical value of 2. The theoretical transmitted ultrasonic power through a polystyrene plate was 88% whereas the experimental values were 86% for lMHz and 71 % for 4MHz ultrasound. Overall, the measured characteristics of the selected transducers were in good agreement with theoretical values. The output ultrasonic powers were also found to be consistent over four months. Tone-burst ultrasound (32 Watt/cm2, 20% Duty Cycle, 50msec burst period) was found to significantly (p<0.01) enhance cytotoxicity when used in combination with 20pM doxorubicin compared to doxorubicin-alone or ultrasound-alone controls. With 30 seconds exposure, immediate cytotoxicity was enhanced by 70% compare to doxorubicin-only control. The long-term cytotoxicity was enhanced by 83% compare to ultrasound-only control. The spatial-peak-temporal-peak ultrasonic power density threshold for cytotoxicity enhancement at 4MHz was 30W/cm ², which translates to minimal actuation amplitude of 112nrn. A Micro-Ultrasonic-Transducer (MUT) must satisfy that minimal actuation amplitude in order to enhance cytotoxicity at 4MHz and be useful for sonodynamic therapy. Tone-burst ultrasound was also found to significantly enhance (p<0.05) cytotoxicity of micellar paclitaxel. The most significant enhancement (53%) was observed with micelles formed with 150yM PDLLA-MePEG diblock copolymers and loaded with 0.1% paclitaxel. The use of ultrasound to enhance cytotoxicity of micellar paclitaxel was found to be another promising application of implantable MUTs.

Text

2010-01-14

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http://hdl.handle.net/2429/18154

Mechanical Engineering

University of British Columbia

UBCV

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