Title :
Model drug delivery by transiently stable microbubbles produced by a microfluidic device
Author :
Dixon, Adam J. ; Dhanaliwala, Ali H. ; Chen, J.L. ; Hossack, John A.
Author_Institution :
Univ. of Virginia, Charlottesville, VA, USA
Abstract :
Ultrasound-mediated drug delivery using intravascular ultrasound (IVUS) and microbubbles holds promise as a potential therapy for diseases of the vasculature. In this work, we evaluate the therapeutic potential of an on-demand microbubble production framework using a flow-focusing microfluidic device to generate microbubbles at the tip of the IVUS catheter for direct administration into the bloodstream. Rat aortic smooth muscle cells were placed in a flow chamber, 8 μm diameter monodisperse microbubbles produced within the flow chamber by a flow-focusing microfluidic device, and ultrasound was applied to enhance uptake of a surrogate drug (calcein). Flow rates up to 18 mL/s and acoustic peak-negative-pressures up to 300 kPa were investigated. Microbubbles produced by the microfluidic device were stabilized with a polyethylene glycol-40-stearate shell and had either a perfluorbutane (PFB) or nitrogen gas core. Calcein delivery was observed at lower acoustic pressures with nitrogen microbubbles than with PFB microbubbles, and maximal delivery occurred at a flow rate of 9 mL/s. These results demonstrate the potential of transiently stable microbubbles produced by a microfluidic device for enhancing localized drug delivery.
Keywords :
bioMEMS; biomedical ultrasonics; blood; catheters; cellular biophysics; diseases; drug delivery systems; haemodynamics; microfluidics; muscle; IVUS catheter; PFB microbubbles; acoustic peak-negative-pressures; bloodstream; calcein delivery; drug; flow chamber; flow-focusing microfluidic device; intravascular ultrasound catheter; localized drug delivery; low acoustic pressures; microbubble production framework; model drug delivery; monodisperse microbubbles; nitrogen gas core; nitrogen microbubbles; perfluorbutane; polyethylene glycol-40-stearate shell; rat aortic smooth muscle cells; transient stable microbubbles; ultrasound-mediated drug delivery; vasculature diseases; Acoustics; Drug delivery; Liquids; Microfluidics; Nitrogen; Production; Ultrasonic imaging; Drug delivery; microbubbles; microfluidics; sonoporation;
Conference_Titel :
Ultrasonics Symposium (IUS), 2013 IEEE International
Conference_Location :
Prague
Print_ISBN :
978-1-4673-5684-8
DOI :
10.1109/ULTSYM.2013.0380