包裹液态氟碳的PLGA微球增强HIFU能量沉积的实验研究

发布时间：2018-07-12 16:05

本文选题：液态氟碳 + 液气相变　；参考：《重庆医科大学》2012年硕士论文

【摘要】：第一部分包裹液态氟碳PLGA微球的制备及体外实验研究目的：制备一种新型超声造影剂—液态氟碳PLGA微球，初步探讨体外液气相转变条件与超声、CT显影效果。方法：采用乳化-蒸发法制备包裹液态氟碳的PLGA微球，光镜、扫描电镜观察微球形态、分布，激光粒度和电位分析仪检测微球粒径、电位。光镜联合体外超声初步探究微球发生液气相转变的条件；观察体外CT显影效果。结果：成功制备了分别包裹PFH和PFOB的PLGA微球。PFH/PLGA微球在水域中逐渐加热达70℃时，光镜及体外超声可见微球随加热温度升高体积逐渐增大、数量逐渐减少，而PFOB/PLGA微球在持续加热达80℃时微球均未见明显形态学及声学变化。体外CT显影， PFOB/PLGA微球组的平均CT值显著高于其它各组，差异有统计学意义。结论：成功制备的液态氟碳高分子微球粒径小，稳定性好，在一定条件下可发生液气转变，有望成为一种新型超声造影剂。第二部分包裹液态氟碳的PLGA微球增强HIFU消融兔肝的实验研究目的：探讨自制包裹液态氟碳的PLGA微球增强高强度聚焦超声（HIFU）体外消融正常牛肝的最佳功率及体内消融正常兔肝脏的疗效。方法：实验分为两部分：第一部分为HIFU消融离体牛肝实验，分别注射四种不同的药物后行HIFU消融，寻找最佳消融功率与时间；分4组：①HIFU+NACL组，②HIFU+PLGA组，③HIFU+PFH组、④HIFU+PFH/PLGA组；第二部分HIFU消融正常兔肝脏实验，同样分为以上四组，分别经兔耳缘静脉注射药物后以相同的参数行HIFU消融，观测并相互比较各组靶区消融前后超声声像图面积，灰阶值，及实际肝脏损伤情况。结果：离体牛肝实验中2、3、4组均在150W、2s出现声像图灰度的变化和肝脏的凝固性坏死；正常兔肝脏实验中，，3、4组靶区的平均超声灰阶值与面积大于1、2组，差异有统计学意义（P0.001），且随时间延长其灰阶值与面积逐渐缩小，而3、4组比较为差异无统计学意义（P0.05）；病理检查1、2组肝脏未见明显损伤，3、4组靶区肝脏见出血性坏死或白色凝固性坏死。结论：包裹液态氟碳的高分子微球可有效增强HIFU的消融效率，为一种较好的HIFU增效剂。
[Abstract]:The first part is the preparation and in vitro study of liquid fluorocarbon PLGA microspheres.
Objective: to prepare a new type of ultrasound contrast agent, liquid fluorocarbon PLGA microspheres, and to preliminarily investigate the conditions of liquid gas phase transformation in vitro and the effects of ultrasound and CT.
Methods: PLGA microspheres containing liquid fluorocarbon were prepared by emulsification and evaporation method. The morphology and distribution of microspheres were observed by light microscopy and scanning electron microscopy. The particle size and potential of the microspheres were detected by the laser particle size and potential analyzer. The conditions for the gas phase transition of microspheres were preliminarily explored by optical microscope combined with in vitro ultrasound, and the effect of CT development in vitro was observed.
Results: when the PLGA microsphere.PFH/PLGA microspheres containing PFH and PFOB were successfully prepared to heat up to 70 degrees in the water, the volume of the microspheres increased gradually with the increase of the heating temperature, and the number of the microspheres gradually decreased with the increase of the heating temperature. And the microspheres had no obvious morphological and acoustic changes when the PFOB/PLGA microspheres were continuously heated up to 80. C in vitro. The average CT of PFOB/PLGA microspheres was significantly higher than that of the other groups in T development, and the difference was statistically significant.
Conclusion: the prepared liquid fluorocarbon polymer microspheres have small particle size and good stability.
Under certain conditions, liquid gas shift can occur and is expected to become a new type of ultrasound contrast agent.
The second part is to study the effect of PLGA microspheres coated with liquid fluorocarbon on HIFU ablation of rabbit liver.
Objective: To investigate the optimal power of PLGA microspheres encapsulated liquid fluorocarbon (HIFU) and high intensity focused ultrasound (HIFU) in the ablation of normal bovine liver in vitro and the effect of in vivo ablation of normal rabbit liver.
Methods: the experiment was divided into two parts: the first part was the HIFU ablation of bovine liver liver test. After injection of four different drugs, the optimal ablation power and time were found, and 4 groups were divided into 4 groups: (1) group HIFU+NACL, group HIFU+PLGA, group HIFU+PFH, group HIFU+PFH/PLGA, and second part of HIFU ablation normal rabbit liver experiment, also divided into two groups. The above four groups were treated with the same parameters for HIFU ablation after the injection of the rabbit ear vein. The ultrasonic image area, gray scale, and the actual liver damage were observed and compared with each other in each group.
Results: in the experimental group of bovine liver, 2,3,4 groups were all in 150W, 2S, and the changes in the gray scale of the image and the coagulative necrosis of the liver. In the normal rabbit liver experiment, the average ultrasonic gray scale value of the target area of the 3,4 group was larger than that of the 1,2 group, and the difference was statistically significant (P0.001), and the gray scale and area of the group were gradually reduced with the time prolonged, while the 3,4 group was compared. The difference was not statistically significant (P0.05); pathological examination showed no obvious damage to liver in group 1,2, hemorrhagic necrosis or coagulating necrosis in liver of group 3,4.
Conclusion: encapsulated liquid fluorocarbon polymer microspheres can effectively enhance the ablation efficiency of HIFU and serve as a better HIFU synergist.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R310

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