Development and evaluation of ultrasound therapeutic system for drug activation

针对药物活化超声治疗系统的研制与评价，研制了多频超声发生器。研究了超声诱导细胞杀伤、增强药物透皮吸收、回声造影剂和模拟回声造影剂增强生物和化学效应、超声基因转移和超声诱导细胞凋亡的频率依赖性。大鼠胸腺细胞碘释放与细胞杀伤的相对比值按频率顺序排列，0.5 MHz>1.0 MHz>38 kHz>2.0 MHz。在饱和ar溶液中，半胱氨酸自由基清除剂存在时，0.5 MHz超声对细胞杀伤有部分保护作用。回声造影剂PVC-AN（聚偏氯乙烯-丙烯腈共聚物）在空气饱和水溶液中通过超氧化物依赖途径增强超声诱导的H_2O_2生成，尽管PVC-AN作为自由基清除剂通过OH自由基的重组来降低H_2O_2的生成。观察到超声诱导的细胞溶解和血栓溶解在PVC-AN存在下增强。观察了超声照射对大鼠乙酰胆碱透皮吸收的增强作用。超声增强HeLa细胞的基因转移和U937细胞凋亡的证据也在超声造影剂Levovist的存在下得到了证实。

Concerning development and evaluation of ultrasound therapeutic system for drug activation, multi-frequency ultrasonic generator was made. Frequency dependence of cell killing induced by ultrasound, enhancement of transdermal absorption of drugs, enhancement of biological and chemical effects by echo contrast agents and an echo contrast agent mimic, ultrasonic gene transfer and apoptosis induced by ultrasound were investigated.1. The relative ratio of iodine release vs. cell killing of rat thymocytes was the order of frequencies, 0.5 MHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed on the cell killing after sonication with 0.5 MHz in Ar-saturated solution in the presence of a free radical scavenger, cysteamine.2. An echo contrast agent mimic, PVC-AN (poly-vinylidene chloride-acrylonitryl copolymer), enhanced H_2O_2 production induced by ultrasound through the superoxide dependent pathway in air-saturated aqueous solution, although PVC-AN acted as a free radical scavenger to lower H_2O_2 formation by recombination of OH radicals. Enhancement of ultrasonically induced cell lysis and thrombolysis in the presence of PVC-AN was observed.3. Enhancement of transdermal absorption of acetylcholine in rat due to ultrasonic exposure was observed.4. Evidence of enhancement of gene transfer in HeLa cells and apoptosis in U937 cells induced by ultrasound in the presence of an echo contrast agent, Levovist, was also obtained.