载脑源性神经营养因子脂质体纳米微粒脂膜微泡超声造影剂的制备与初步评价  

Preparation and primary evaluation of brain-derived neurotrophic factor liposome nanoparticles-loaded microbubbles as ultrasound contrast agent

作　　者：程伟 赵大威[1] 田猛[1] 胡加银 阳建政 杜鹏[1] 王翔[1] CHENG Wei;ZHAO Dawei;TIAN Meng;HU Jiayin;YANG Jianzheng;DU Peng;WANG Xiang(Department of Ultrasound,Daping Hospital & Institute of Surgery Research,Army Medical University,Chongqing 400042,China)

机构地区：[1]陆军军医大学大坪医院野战外科研究所超声科,重庆市400042

出　　处：《临床超声医学杂志》2018年第4期217-220,共4页Journal of Clinical Ultrasound in Medicine

基　　金：重庆市自然科学基金资助项目(cstc2014jcyj A10103)

摘　　要：目的制备一种新型的载脑源性神经营养因子(BDNF)脂质体纳米微粒脂膜微泡超声造影剂(BDNF-UMCA),并对其应用进行初步评价。方法以冷冻干燥法在"脂氟显"制备的基础上加入与二棕榈酰磷脂酰胆碱等量的含生物素化棕榈酰磷脂酰甘油钠-聚乙二醇2000-生物素,制备含生物素化脂膜超声微泡造影剂,通过链亲和素耦连含生物素化聚乙二醇载BDNF脂质体纳米微粒制备BDNF-UMCA,检测其物理性质、载药量、包封率、稳定性及体内声学特性。结果 BDNF-UMCA平均粒径(4.20±0.79)μm,浓度1.02×109/ml,总药物含量(1.18±1.96)mg/ml,包封率(71.6±2.6)%。在4℃下,BDNF-UMCA平均粒径和包封率各时间点无明显变化;在(24±2)℃下,BDNF-UMCA的平均粒径随时间推移逐渐增大,第1、3、5、7天的粒径与初始粒径比较差异均有统计学意义(均P<0.05),包封率在(24±2)℃下各时间点比较差异无统计学意义。BDNF-UMCA能显著增强实验动物肝脏显影,平均峰值强度(21.5±3.5)d B,平均达峰时间(19.2±5.2)s。结论应用生物素-亲和素耦连可成功制备BDNF-UMCA;BDNF-UMCA可为靶向显影及药物通过血脑屏障释放提供工具。Objective To explore the preparation of a new type of brain-derived neurotrophic factor(BDNF) liposome nanoparticles-loaded lipid ultrasound microbubble contrast agent(BDNF-UMCA),and to preliminarily evaluate its application. Methods Ultrasound microbubbles contrast agent(UMCA) were prepared by adding a certain proportion of DPPG-PEG(2000)-biotin based on“Zhifuxian” using cryochem and mechanical agitation method,BDNF-UMCA were prepared by coupling with biotinylated BDNF-loaded liposome nanoparticles via streptavidin.The physicochemical properties,drug loading,entrapment efficiency,stability and acoustic characteristics of BDNF-UMCA in vivo were tested.Results The average diameter of BDNF-UMCA was(4.20±0.79)μm,the concentration was 1.02×109/ml,and the total drug content was(1.18±1.96) mg/ml,the entrapment efficiency was(71.6±2.6)%.The average size and entrapment efficiency of BDNF-UMCA were not significantly changed at 4℃at different time.The average size of BDNF liposome nanoparticle increased gradually at(24±2)℃,there was difference at day 1,day 3,day 5 and day 7 compared with initial particle size(all P<0.05).While there was no significant difference of the entrapment efficiency at different time at(24±2)℃. BDNF-UMCA could significantly enhance the contrast imaging of experimental animal liver with the average peak strength of(21.5±3.5)dB and the average peak time of(19.2±5.2)s. Conclusion BDNF-UMCA can be successfully prepared by biotin-avidin conjugation method,and it will provide a tool for targeted imaging and drug delivery through blood brain barrier.

关 键 词：超声检查 造影剂 脑源性神经营养因子 生物素 脂质体 微泡 血脑屏障 

分 类 号：R445.1[医药卫生—影像医学与核医学]