Ultrasound degradation of novel polymer contrast agents

This report describes an investigation into factors affecting the degradation of novel poly(lactic-co-glycolic acid) (PLGA) contrast agents. Contrast agents fabricated by two different methods and varying in acoustic properties were compared. The effect of ultrasound frequency (5 and 10 MHz) on degradation of the microcapsules was also studied. High-performance liquid chromatography was used to quantify the production of lactic and glycolic acid to monitor agent degradation. The degradation pattern from the microcapsules was found to be closely related to capsule morphology; the more acoustically efficient capsules (maximum enhancement of 25 dB at 5 MHz with 0.004 mg/mL) degraded at a faster rate than those with lower acoustical efficiency (maximum enhancement of 25 dB at 5 MHz only achieved with 0.6 mg/mL). The capsules also degraded fastest when insonated at the frequency at which they gave highest backscatter. In addition, despite the use of a 50:50 PLGA copolymer, more glycolic than lactic acid was released at early time points, which reflects the greater hydrophilicity of the glycolic acid residues, and greater degradation rate of glycolic acid repeat units. The results from this study provided unique insight into the degradation behavior of hollow PLGA microcapsules, and their potential in ultrasound diagnosis and therapy.