上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (9): 1024-.doi: 10.3969/j.issn.1674-8115.2010.09.002

• 专题报道（影像医学与核医学） • 上一篇    下一篇

可携基因超声造影剂的制备及其体内外显影效果

李殿城1, 朱家安1, 郭 微2, 刘 芳1, 徐宇虹2, 胡 兵1   

  1. 1.上海交通大学附属第六人民医院超声医学科 上海超声医学研究所, 上海 200233；2.上海交通大学 药学院, 上海 200240
  • 出版日期:2010-09-25 发布日期:2010-09-27
  • 通讯作者: 朱家安, 电子信箱: zhuja@sjtu.edu.cn。
  • 作者简介:李殿城（1985—）, 男, 硕士生；电子信箱: lidiancheng1985@126.com。
  • 基金资助:

    国家自然科学基金（30970794）；上海市自然科学基金（09ZR1424300）；上海交通大学医工结合课题（YG2009MS32）

Preparation of gene-loaded ultrasound contrast agent and its in vitro and in vivo enhancement effects

LI Dian-cheng1, ZHU Jia-an1, GUO Wei2, LIU Fang1, XU Yu-hong2, HU Bing1   

  1. 1.Department of Ultrasound in Medicine, The Sixth People's Hospital, Shanghai Jiaotong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, China；2.School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, |China
  • Online:2010-09-25 Published:2010-09-27
  • Supported by:

    Natural Science Foundation of China, 30970794；Natural Science Foundation of Shanghai, 09ZR1424300；Shanghai Jiaotong University Foundation, YG2009MS32

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摘要：

目的 制备一种新型的超声造影剂，研究其理化性质及体内、外显影效果。方法 选用体内可降解的两种脂质体二软脂酰卵磷脂（DPPC）和1，2-二油烯氧基-3-三甲氨基丙烷（DOTAP），采用薄膜分散法制备超声造影剂，观察其外观和形态及粒径分布。以声诺维超声造影剂、PBS和水合液作为对照组，比较其基因携带能力。采用体内、外显影实验，观察自制超声造影剂的显影效果和时间。结果 光学显微镜下显示，自制超声造影剂形态规则，呈球形，大小均一，平均粒径为6.969 μｍ。自制超声造影剂与声诺维超声造影剂相比有较好的基因携带能力，而声诺维超声造影剂与PBS及水合液的携基因能力无明显差异。体外超声显影显示，自制超声造影剂在Skeletal muscular模式下显影时间为18 min，造影模式下显影时间为14 min，两种模式下管内均表现为强回声，有很好的影像增强效果；体内超声显影（造影模式）显示，大鼠尾静脉注射造影剂后1 s时下腔静脉开始显影，3 s时腹主动脉中下段开始显影，内均可见强回声充填。结论 脂质体包裹的微泡理化性质稳定，具有较好的基因携带能力，体内外显影效果较好，有望成为一种新型的可携带基因和药物的超声造影剂。

关键词: 超声造影剂, 微泡, 脂质体, 阳离子脂质体, 声诺维

Abstract:

Objective To prepare a new ultrasound contrast agent, and investigate its characteristics and in vitro and in vivo enhancement effects. Methods Two kinds of liposome, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were selected to prepare ultrasound contrast agent by film dispersion method, and its appearance, morphology and particle diameter were observed. The gene-loaded capability of prepared ultrasound contrast agent was compared with SonoVue ultrasound contrast agent, PBS and hydration liquid. The in vitro and in vivo enhancement effects of prepared ultrasound contrast agent were observed. Results The prepared ultrasound contrast agent was ball-shaped, with regular and uniform morphology and mean particle diameter of 6.969 μm. The gene-loaded capability of prepared ultrasound contrast agent was better than that of SonoVue ultrasound contrast agent, while there was no significant difference between SonoVue ultrasound contrast agent and PBS and hydration liquid. In vitro ultrasound imaging revealed that the enhancement time of prepared ultrasound contrast agent under Skeletal muscular mode was 18 min, that under contrast mode was 14 min, and dense echo with favourable enhancement effects was found under both modes. In vivo ultrasound imaging (contrast mode) revealed that imaging of inferior caval vein and middle-inferior segment of abdominal aorta began to develop 1 s and 3 s, respectively after injection of contrast agent into rat tail vein, with dense echo for both. Conclusion Liposome-coated microbubbles are stable with favourable gene-loaded capability, and may serve as a new ultrasound contrast agent for loading genes or drugs.

Key words: ultrasound contrast agent, microbubble, liposome, cationic liposome, SonoVue