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Ultrasound-triggered Release from Micelles

Ultrasound is an ideal trigger for site-actuated drug delivery because it can be focused through the skin to internal targets without surgery. Thermal or mechanical energy can be delivered via tissue heating or bubble cavitation, respectively. Bubble cavitation, which concentrates energy that can trigger drug release from carriers, occurs more readily at low frequencies and at bubble resonant frequencies. Other mechanical and physical consequences of cavitation are reviewed. Micelles are nanosized molecular assemblies of amphiphilic molecules that spontaneously form in aqueous solution and possess a hydrophobic core capable of sequestering hydrophobic drugs. Micelles have traditionally been used to increase the solubility of hydrophobic therapeutics for oral and intravenous administration. For ultrasonic drug delivery, polymeric micelles containing polyethylene oxide blocks are preferred because they have longer circulation time in vivo. Passive delivery occurs when micelles accumulate in tumor tissues that have malformed capillaries with porous walls. In active delivery targeting ligands are attached to the micelles, which directs their binding to specific cells. Actuated delivery occurs when ultrasound causes drug release from micelles and is attributed to bubble cavitation since the amount released correlates with acoustic signatures of cavitation. The mechanisms of ultrasonic drug release are discussed, including the prevalent theory that gas bubble cavitation events create high shear stress and shock waves that transiently perturb the structure of the micelles and allow drug to escape from the hydrophobic core. Ultrasound also perturbs cell membranes, rendering them more permeable to drug uptake. Tumors in rats and mice have been successfully treated using low-frequency ultrasound and chemotherapeutics in polymeric micelles. Ultrasonically activated drug delivery has great clinical potential.

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17 Apr 2013
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From the book series:
Smart Materials Series