用于超声造影成像的颗粒稳定气泡制备  

Preparation of particle stabilized bubbles for contrast ultrasound imaging

作　　者：张晴 吴颉[1,2] 马光辉 Qing ZHANG;Jie WU;Guanghui MA(National Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China;School of Chemical Engineering,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [2]中国科学院大学化学工程学院,北京100049

出　　处：《过程工程学报》2022年第6期828-838,共11页The Chinese Journal of Process Engineering

基　　金：国家自然科学基金资助项目(编号:22078335,21776287)。

摘　　要：超声成像由于其无创无痛、可实时监测以及成本低廉等优点,被广泛用于多种疾病诊断。但是,某些人体组织回声较弱,需要借助具有强回声特性的超声造影剂微气泡来实现对比成像。目前临床批准使用的微气泡多采用表面活性剂或磷脂作为稳定剂,其稳定效果有限、血液循环时间短,限制了对小病灶等需要长时间观察的病变部位的检查能力。颗粒稳定气泡(Particle Stabilized Bubbles,PSBs)是由颗粒代替传统表面活性剂稳定的气泡,由于其具有高稳定性、低毒性等优势,有望用于超声造影。但目前关于颗粒稳定气泡的制备及应用研究较少,其原因主要在于体系对颗粒的接触角范围要求很窄,一旦超过界定范围,则气泡稳定性急速下降。本工作以制备出稳定的颗粒稳定气泡,考察其作为超声造影剂的效果为目标。通过筛选不同亲疏水性的颗粒作为稳定剂,并对其荷电性、浓度、粒径、水相及气相等因素进行考察,制备得到了由壳聚糖纳米颗粒(CNPs)稳定的颗粒稳定气泡(CPSBs)。并在此基础上,通过细胞毒性实验、溶血性、病理切片等实验评价了体系的生物安全性,通过小动物超声成像仪考察了其体内外造影性能。实验结果表明该体系具有良好的生物安全性以及良好的体内外造影能力,表明其具有作为超声造影剂应用的潜力。Ultrasound imaging is widely used in the diagnosis of a variety of diseases due to its plenty of advantages,such as non-invasive,painless,real-time monitoring and low cost.However,some issues are with weak echoes.As a result,it is necessary to enhance the ability of ultrasound imaging by using an ultrasound contrast agent(microbubbles)with strong echo characteristics.At present,most of the microbubbles approved for clinical use consist of surfactants or phospholipids.Because of their strong compressibility,these bubbles can enhance the ultrasonic Doppler signal of blood flow and improve the clarity and resolution of ultrasonic images.But they still have some disadvantages,such as their limited stabilization effect and short blood circulation time,which limits the ability to inspect lesions that need long-term observation such as small lesions.Particle stabilized bubbles(PSBs)are bubbles formed by particles instead of surfactants stabilizing the gas-liquid interface.Compared with surfactant stabilized bubbles,the PSBs system has higher stability,because the particles are irreversibly adsorbed at the gas-liquid interface,which makes them a great potential ultrasound contrast agent.However,there are few studies on the preparation and application of particle-stabilized bubbles.The main reason is that the system requires a very narrow range of contact angles for particles.Once the range exceeds the defined range,the bubbles will burst rapidly.This work aims to prepare stable PSBs and to solve the problem of lacking research on PSBs at present.In this experiment,we did an extensive screening of different hydrophilic and hydrophobic particle stabilizers,then we investigated the influence of their charge,concentration,particle size,water phase and gas equal factors in forming PSBs.Finally,we prepared PSBs stabilized by chitosan nanoparticles(CNPs).On this basis,the biocompatibility of the system was evaluated by cytotoxicity test,hemolysis test and pathological section test.The contrast-enhanced performance of the system

关 键 词：颗粒稳定气泡 超声造影剂 造影能力 生物安全性 

分 类 号：TQ421.7[化学工程]