包裹阿霉素的高分子材料微泡声学造影剂制备及显影效果实验研究

Research on fabrication of high molecular polymer ultrasound contrast agent for drug delivery

目的探索包裹药物的微泡声学造影剂制备方法,观察其体内外显影效果。方法采用在体内能生物降解的人工合成高分子聚合物乳酸/羟基乙酸共聚物(PLGA)作为成膜材料,通过双乳化法和冷冻干燥技术制备包裹阿霉素(ADM)和空气的PLGA微泡声学造影剂(ADM-PLGA声学造影剂)。光学显微镜进行形态学观察。体外和动物实验观察其显影效果。结果采用本法成功制备了ADM-PLGA声学造影剂;光镜观察其形态规则,呈球型,大小均匀,最大粒径<4μm;体内外显影效果好。结论通过本方法可以合成包裹水溶性药物的微泡声学造影剂,为应用超声波和微泡造影剂进行体内药物定位释放研究打下了基础。

Objective To develop High Molecular Polymer Ultrasound Contrast Agent for drug delivery; To study the effect on ultrasound imaging, and to quantify drug encapsulation efficiency and drug loading amounts. Methods PLGA, a novel artificial and biodegradable high molecular polymer- poly lactic - co - glycolic acid, was employed to fabricate the ultrasound contrast agent with Adriamycin （ADM） and air inside by a double emulsion method and lyophilizafion method. Light microscope was used to study the shape and surface morphology of the ADM- PLGA contrast agent. UV- Vis Spectrophotometer was used to quantify drug encapsulation efficiency and drug loading amounts. Then experiments in vitro and in vivo were employed to study the effects of ADM - PI_GA contrast agent on the enhancement of ultrasound imaging. Results This method could produce uniformly ADM- PIGA ultrasound contrast agent with a tight size distribution and smooth surface, which were determined under the light microscope. It was an effective ultrasound contrast agent both in vitro and vivo. The drug loading amounts was about 5.46% （mg/g） ,and drug encapsulation efficiency was 68.25%. Conclusion This method could produce an ultrasound contrast agent for drug delivery. Because of its potential ability of releasing drug to targeted place by using ultrasound, it must have a bright future in application field.