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Digital Drug Delivery: On-Off Ultrasound Controlled Antibiotic Release from Coated Matrices with Negligible Background Leaching.

Hydrogels, such as crosslinked poly(2-hydroxyethyl methacrylate) (pHEMA) have been used extensively in controlled release drug delivery systems. Our previous work demonstrated an ultrasound (US)-responsive system based on pHEMA coated with a self-assembled multilayer of C12-C18 methylene chains. The resulting coating was predominantly crystalline and relatively impermeable, forming an US-activated switch that controlled drug release on-demand, and kept the drug within the matrix in the absence of US. The device, as developed did, however, show a low background drug-leaching rate independent of US irradiation. For some applications, it is desirable to have very low or zero background release rates. This was achieved here by a combination of new processing steps, and by copolymerizing HEMA with a relatively hydrophobic monomer, hydroxypropyl methacrylate (HPMA). These advances produced systems with undetectable ciprofloxacin background release rates that are capable of US-facilitated drug release - up to 14-fold increases relative to controls both before and after US exposure. In addition, these observations are consistent with the hypothesis that US-mediated disorganization of the coating allows a transient flux of water into the matrix where its interaction with bound and dissolved drug facilitates its movement both within and out of the matrix.