载硫化氢气体超声微泡的制备及其性能评价  

Preparation and characterization of microbubbles loaded with hydrogen sulfide

作　　者：陈钢彬 杨莉[2] 李新忠[1] 钟林涛[1] 吴爵非[1] 宾建平[1] 

机构地区：[1]南方医科大学南方医院心内科,广东广州510515 [2]南方医科大学南方医院药学部,广东广州510515

出　　处：《南方医科大学学报》2015年第12期1672-1677,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(81101064);广州市科技计划项目(201506010021)~~

摘　　要：目的制备一种新型的载硫化氢气体的脂质微泡(HSMB)并评价其理化特性和超声显影能力。方法硫化氢和全氟丙烷按4∶0、3∶1、2∶2、1∶3和0∶4混合后,机械震荡法制备5种载相应混合气体的HSMB,即HSMB4∶0、HSMB3∶1、HSMB2∶2、HSMB1∶3和HSMB0∶4。检测微泡的粒径及浓度并评价其稳定性,优化气体混合比例。选取优化的混合气体制备的HSMB,观察超声辐照对微泡浓度及下清液中硫化氢浓度的影响;观察大鼠心肌及肾脏的超声显影效果。结果 HSMB外观呈乳白色,镜下呈球形结构,无聚集现象。HSMB4∶0和HSMB3∶1微泡初始浓度较HSMB2∶2明显减少(P<0.05),且均随时间的延长逐渐降低。HSMB2∶2、HSMB1∶3和HSMB0∶4微泡初始浓度无差别(P>0.05),72 h内浓度无变化(P>0.05)。超声辐照后,HSMB2∶2微泡浓度显著减少(P<0.05),而下清液中的硫化氢浓度明显增加(P<0.05)。HSMB2∶2静脉注射后获得良好的心脏及肾脏超声显影效果。结论硫化氢和全氟丙烷以2∶2混合制备的HSMB浓度高、稳定性良好,可在超声辐照下释放硫化氢,具有良好的超声显像效果,有望实现硫化氢气体可视化靶向传输。Objective To prepare a phospholipid- coated microbubble loaded with hydrogen sulfide（HSMB） and evaluate its physicochemical and acoustic properties. Methods Hydrogen sulfide and perfluoropropane were mixed at the ratios of 4：0, 3：1, 2：2, 1：3, and 0：4 to prepare hydrogen sulfide-loaded microbubbles（termed HSMB4：0, HSMB3：1, HSMB2：2, HSMB1：3, and HSMB0：4,respectively）. The microbubble concentration and diameter were investigated and their stability were evaluated. The optimal ratio of hydrogen sulfide and perfluoropropane was determined according to the changes of microbubble concentration. The changes of dissolved hydrogen sulfide and concentration of the microbubbles were investigated after exposure to ultrasound,and their acoustic enhancement effects in the myocardium and kidney were observed after intravenous injection in rats.Results HSMBs were milky in color and spherical in shape without aggregations. The concentrations of HSMB4：0and HSMB3：1were lower than that of HSMB2：2and decreased with time. HSMB2：2, HSMB1：3and HSMB0：4showed comparable concentrations and were stable within 72 h. After exposure to ultrasound, the concentration of HSMB2：2decreased while the dissolved hydrogen sulfide increased significantly. Intravenous injection of HSMB2：2produced a satisfactory contrast-enhancing effect in the myocardium and kidney of rats. Conclusion HSMB prepared with the hydrogen sulfide to perfluoropropane ratio of 2：2has excellent contrast-enhancing effect and is capable of carrying and releasing hydrogen sulfide upon ultrasound exposure to potentially allow visual site-specific delivery of hydrogen sulfide.

关 键 词：微泡 超声 硫化氢 

分 类 号：R943[医药卫生—药剂学]