载血卟啉的乳酸／羟基乙酸共聚物超声微泡造影剂制备及工艺优化

Preparation of hematoporphyrin-loaded PLGA ultrasound microbubble and optimization of formulation

目的探讨载声敏剂血卟啉（hematoporphyrin，HP）的高分子材料乳酸／羟基乙酸共聚物EPoly（1actic—CO—glycolicacid），PLGA~超声微泡造影剂的优化制备工艺。方法采用双乳化法制备包裹HP的PLGA超声微泡造影剂，通过正交设计筛选出比较理想的制备工艺，并对所制备的造影剂进行药物体外释放评估及体外超声造影观察。结果载HP的PI．GA造影剂（HP—PLGA）平均粒径602．3nm，平均包封率63．5％，平均载药量2．15％，电位-（17．1±1．6）mV，体外14d缓释约86．5％，体外超声显影良好。结论通过采用双乳化法制备的HP-PLGA造影剂，具备缓释长效的特性，体外显像效果好，符合理想药物载体的基本特性，为实时监控下体内声动力治疗肿瘤提供了一种新型的药物剂型。

Objective To optimize the formulation of a new kind of ultrasound contrast agents carrying the sensitizer of hematoporphyrin （HP） with [ Poly （ lactic co glycolic acid）, PLGA] for material. Methods The technique of double emulsion was applied to produce HP loaded PLGA ultrasound mierobubbles, which was optimized through orthogonal test using encapsulation efficiency for the detected index. Then morphology and distribution of HP-PLGA microbubbles were observed through light microscope and scaning electron microscope. The size,Zeta potential and the properties of releasing behavior and ultrasound imaging in vitro of HP PLGA contrast agents were detected. Results The optimization parameters were picked out as 1（） mg/ml for concentration of HP,40 mg for PLGA,and 1/5 for volume ratio of water inside to dichloromethane. The optimized HP-PLGA contrast agents were spheric with the mean size of 602.3 nm,and Zeta potential of - （17. 1 ± 1.6） mV. The drug loading and encapsulation efficiency of HP-PLGA were （2.15± 0.15）% and （63.5±2.6）%, respectively. And the releasing behavior of HP-PLGA contrast agents in vitro was that after an obvious release of about 35.1 % in former 24 h, there were 86.5 % HP-PLGA released within 14 days. The ultrasound imaging of HP-PLGA could be enhanced obviously in vitro. Conclusions The self-made HP PLGA ultrasound microbubble might be % useful tool for delivering sensitizer and thus provide a novel strategy for sonodynamic therapy on tumor.