Optimization research on preparation conditions of polymer-shelled microbubble contrast agents / 中国组织工程研究

ABSTRACT

BACKGROUND:In previous experiments, a polymer-shel ed microbubble contrast agent was successful y prepared using L-polylactic acid-polyethylene glycol methyl-covered liquid fluorocarbon perfluoropentane, which developed wel in vivo and in vitro under a second harmonic contrast-enhanced ultrasound with a low mechanical index OBJECTIVE:To optimize the conditions for preparing polymer-shel ed microbubble contrast agents with high yield and suitable size. METHODS:The polymer-shel ed microbubble contrast agent containing perfluoropentane was prepared by single emulsion method. Three preparation conditions, including polymer mass/perfluoropentane volume ratio (4/1, 2/1, 1/1, 1/2), hemogenate speed (18 000, 26 000, 35 000 r/min) and time (15, 30, 60, 120 seconds), were optimized, and the microbubble yield and size were set as judge standard. The contrast-enhanced ultrasonography of rabbit kidney was performed using the optimized microbubbles, and the arrival time, time to peak, half time of descending and peak intensity were analyzed by TCA software. RESULTS AND CONCLUSION:The preparation conditions were optimized as a polymer mass/perfluoropentane volume ratio of 2/1, homogenate speed of 26 000 r/min and homogenate time of 60 seconds, which presented a high microbubble yield of (1.8±0.4)×109/mL and mean size of (3.7±1.3)μm with uniform distribution. The arrival time, time to peak, half time of descending and peak intensity were detected as (3.1±0.6) seconds, (2.9±0.5) seconds, (4.0±0.7) seconds and (4.7±1.1)×10-5 AU, respectively. The polymeric microbubbles prepared by optimized conditions were of high yield, with suitable size and good contrast-enhanced effect in vivo.