| 摘要: |
| 目的 探索制备一种新型的耦连包载BDNF脂质体纳米颗粒的脂膜微泡超声造影剂(BDNF-UMCA)。方法 以冷冻干燥法在“脂氟显”制备的基础上加入一定比例的含生物素化棕榈酰磷脂酰甘油钠-聚乙二醇2000-生物素[DPPG-PEG(2000)-Biotin]制备含生物素的脂质超声微泡造影剂,通过链亲和素来耦连含生物素化PEG载BDNF脂质体纳米微粒制备BDNF-UMCA,检测其理化性质、载药量、包封率、稳定性和体内声学特性进行检测。结果 BDNF-UMCA平均粒径4.2±0.79 μm,浓度为1.02×109/ml；总药物含量为1.18±1.96 mg/mL,包封率为71.6±2.6%；BDNF-UMCA在4℃条件下,平均粒径和包封率均无明显的变化；在24℃条件下,载BDNF脂质体纳米微粒的平均粒径随时间逐渐增大,第1、3、5、7天的粒径与初始粒径比较具有明显的统计学差异(均P<0.05),包封率在24℃下各个时间点无明显的统计学差异(均P>0.05)；BDNF-UMCA能显著增强实验动物肝脏显影,平均峰值强度为21.4±0.9 dB,平均达峰时间为4.7±0.4 s。结论 应用生物素-亲和素偶联可成功制备载BDNF脂质体纳米微粒的脂膜超声微泡造影剂,为靶向显影及药物通过血脑屏障释放提供工具。 |
| 关键词: 脑源性神经营养因子 生物素 脂质体 微泡 超声造影剂 血脑屏障 |
| DOI： |
| 投稿时间：2018-01-04修订日期：2018-01-23 |
| 基金项目:重庆市自然科学基金资助项目(cstc2014jcyjA10103) 超声介导新型载BDNF超声微泡治疗缺血性脑卒中的实验研究 |
|
| Preparation and primary evaluation of BDNF liposome nanoparticles-loaded ultrasound microbubbles contrast agent |
| Cheng Wei,Wang Xiang |
| () |
| Abstract: |
| Objective To explore the preparation of a new type BDNF liposome nanoparticles-loaded lipid ultrasound microbubble contrast agent (BDNF-UMCA) . 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; its physicochemical properties and the drug loading, entrapment efficiency, stability and acoustic characteristics in vivo were tested. Results The BDNF-UMCA had the average diameter of 4.2 ± 0.79 m, concentration of 1.02 × 109/ml, and the total drug content of 1.18 ± 1.96 mg/mL, the entrapment efficiency of 71.6 ± 2.6%. The average particle size and entrapment efficiency of BDNF-UMCA were not significantly changed at 4℃; the average particle size of BDNF liposome nanoparticle increases gradually over time at 24℃, there were statistically significant difference at 1, 3, 5 7 compared with initial particle size (all P<0.05); the entrapment efficiency were no statistically significant difference at each time (all P>0.05). BDNF-UMCA can significantly enhance the contrast imaging of experimental animal liver, having the average peak strength of 21.4 ± 0.9 dB and the average peak time of 4.7 ± 0.4 s. Conclusions Using Biotin-avidin conjugation method can be successfully prepared BDNF liposome-loaded ultrasound microbubbles contrast agents as a tool for targeted imaging and drug release through blood brain barrier. |
| Key words: Brain-derived neurotrophic factor Biotin Liposome Microbubbles Ultrasound contrast agents Blood brain barrier |
