载索拉非尼-阿霉素智能控释纳米液滴制备及其超声响应性的实验研究  

Preparation of sorafenib and doxorubicin loaded nanodroplets and its ultrasound-sensitive in vitro：experimental study

作　　者：谭洋[1] 谢晓燕[1] 王伟[1] 郭焕玲 黄通毅 郑巧 徐明[1] 吕明德[1] 

机构地区：[1]中山大学附属第一医院超声科中山大学超声诊断与介入超声研究所,广州510080

出　　处：《中华超声影像学杂志》2017年第10期906-910,共5页Chinese Journal of Ultrasonography

基　　金：广东省医学科研基金（132014123）;国家自然科学基金（81371555）

摘　　要：目的制备一种载索拉非尼一阿霉素双药相变型纳米液滴（sorafenib/doxorubicin loaded nanodroplets, SF/DOX NDs）超声造影剂，并考察其超声响应性。方法采用薄膜水化法制备SF／DOXNDs，测量其粒径、电位及包封率等基本特征。通过体内外观察NDs的超声造影效果及光学显微镜观察，评估NDs在超声转染仪作用下的液气相转变能力。通过体外超声显像及透射电镜观察，验证NDs在超声转染仪作用下产生空化效应。结果SF／DOXNDs呈球形，平均粒径（498±67．34）nm，Zeta电位-（38．87±3．78）mV，SF包封率为（58．14±2．93）％，DOX包封率为（51．23±4．11）％。SF／DOXNDs在体内外均有明显的超声造影效果，证明其能在超声转染仪辐照下相转变形成微泡；给予高强度或持续超声刺激后，NDs产生空化效应破裂并释放药物。结论本实验成功制备了载双药相变型纳米液滴，其联合超声辐照不仅能形成微泡增强超声显像，还可产生空化效应释放药物，为下一步靶向肿瘤组织显像及精准治疗提供了基础。Objective To prepare ultrasound （US） responsive nanodroplets （NDs） simultaneously loaded with anticancer drug Sorafenib （SF） and Doxorubicin （DOX）, and to characterize its ultrasound responsibility in vitro and in vivo. Methods The SF/DOX NDs were prepared using the thin-film hydration method. The particle diameter, Zeta potential and drug-encapsulation efficiency were characterized. The acoustic droplets vaporization activity was monitored hy in vitro ultrasound imaging and light microscope. The cavitation effect was monitored by in vitro ultrasound imaging and transmission electron microscopy. Results SF/DOX NDs were round in shape, the mean diameter and Zeta potential of SF/DOX NDs was （498 ±67.34）nm, - （38.87 ±3.78）mV, respectively. The entrapment efficiency of SF and DOX was （58.14 ± 2.93） %, （51.23 ± 4.11 ） %, respectively. SF/DOX NDs underwent a phase transition into bubbles and could be continuously imaged for more than 25 min in vitro, and afterward therapeutic ultrasound pulse induced inertial cavitation and substantially enhanced treatment. Conclusions US-responsible SF/DOX NDs are prepared using thin-film hydration mehtod, it can enhance ultrasonic echo in vitro and release anticancer drug by the aid of US exposure, which possesses greater researching and applicating value.

关 键 词：超声造影 纳米液滴 液气相转变 

分 类 号：R445.1[医药卫生—影像医学与核医学]