The effect ofultrasound on the degradation of polymers and the release rate of incorporated molecules within those polymers was examined. Up to 5-fold reversible increases in degradation rate and up to 20-fold reversible increases in release rate of incorporated molecules were observed with biodegradable polyanhydrides, polyglycolides, and polylactides. Up to 10-fold reversible increases in release rate of incorporated molecules within nonerodible ethylene/vinyl acetate copolymer were also observed. The release rate increased in proportion to the intensity of ultrasound. Temperature and mixing were relatively unimportant in effecting enhanced polymer degradation, whereas cavitation appeared to play a significant role. Increased release rates were also observed when ultrasound was applied to biodegradable polymers implanted in rats. Histological examination revealed no differences between normal rat skin and rat skin that had been exposed to ultrasonic radiation for 1 hr. With further study, ultrasound may prove useful as a way of externally regulating release rates from polymers in a variety of situations where on-demand release is required.We report here a way to enhance the degradation of solid polymers and the transport ofincorporated substances within polymers. This method involves the exposure of the solid polymer to ultrasound. We also report experiments conducted to elucidate the mechanism of this phenomenon and to explore the therapeutic potential of this method for delivering incorporated substances in vitro and in vivo.MATERIALS AND METHODS Materials. All chemicals were reagent grade. p-Nitroaniline (PNA) and p-aminohippuric acid (PAH) were from Aldrich. Methoxyflurane was from Pitman-Moore (Washington Crossing, NJ). The aquasonic gel used for skin application was therasonic coupling medium from EM Science (Cherry Hill, NJ). Poly(lactic acid) and poly(glycolic acid)were from Polysciences (nos. 6529 and 6525, respectively). Polyanhydrides were synthesized as described (1) In Vitro Experiments. The polylactides and polyglycolides were film-cast at room temperature with PNA in chloroform and 1,1,1,3,3,3-hexafluoro-2-propanol, respectively. The PNA-loaded films were then ground, sieved (90-150 gm), and compression-molded into circular disks in a Carver test cylinder (Menomonee Fall, WI) at 30,000 psi (1 psi = 6.89 kPa) and room temperature for 10 min (3). The polyanhydrides, ground and sieved into a particle size range of ,am, were mixed manually with PNA sieved to the same size range. The mixture was compression-molded into circular disks (14 mm in diameter, 1 mm thick) in a Carver test cylinder at 30,000 psi and 100'C, for poly[bis(p-carboxyphenoxy)methane] (PCPM), and room temperature, for copolymers of bis(p-carboxyphenoxy)propane with sebacic acid (PCPP/SA). In all cases, the polymer disks were loaded with 10% (wt/wt) PNA. The polymer erosion and drug release kinetics were followed by measuring the UV absorbance of the periodically changed buffer solutions in a Perkin-Elmer 553 spectrophotome...
