超声联合新型脑靶向免疫脂质体-微泡载药体系提高跨BBB给药效率的实验研究

项目名称： 超声联合新型脑靶向免疫脂质体-微泡载药体系提高跨BBB给药效率的实验研究

项目编号： No.81201066

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 汪峰

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 血脑屏障（BBB）是中枢神经系统疾病治疗的瓶颈，探索一种既能通过体循环，又能跨越BBB的脑靶向载药体系是业者追求的目标。申请人提出联合超声微泡和免疫脂质体各自优点，构建一种具备靶向识别、有效载药和声学可控的新型脑靶向脂质体微泡载药体系（载药免疫脂质体-微泡复合物）。利用免疫脂质体生物学靶向性使复合物富集在靶区，以超声辐照靶区，使微泡破裂靶向开放BBB，同时促使药物释放、弥散和内皮细胞胞吞增加提高跨BBB给药效率。在已成功构建载药脑靶向脂质体微泡复合物基础上，以C6胶质瘤大鼠模型为研究对象，采用激光共聚焦、电镜、RT-PCR和western-blot等技术，重点对超声介导的声学靶向、BBB受体介导的生物学靶向、总体给药效率及治疗效果进行研究，其结果不仅拓展超声生物学效应和超声/微泡治疗学的研究，还揭示超声/微泡促进BBB开放机制，尤其跨细胞通路机制，为超声在CNS疾病治疗提供新的依据。

中文关键词： 血脑屏障；超声相变纳米粒；胶质瘤；转铁蛋白；载药系统

英文摘要： The blood brain barrier (BBB) has been a bottleneck in the treatment of central nervous system (CNS) disease. Exploring a drug delivery system which can not only through the systemic circulation, but also across the BBB is our aim.The applicant proposed to build a new brain targeting immunoliposome microbubble drug delivery system（Tf- DOX-PLs microbubble complexes）with target identification, the effective drug delivery and acoustic controllable based on the characteristics of microbubble and liposome. We can exploit that the combination of ultrasound and drug delivery system mediated BBB disrupt as well as the biological targeting of immunoliposome to improve the efficiency of drug delivery crossing the BBB. To investigate the acoustic target，receptor-mediated biological targeting and the efficiency of drug administration of the Tf- DOX-PLs microbubble complexes with the help of ultrasonication on C6 glioma in rats, based on the successful construction of the drug delivery system. The study not only expands the research of Ultrasound biological effects and ultrasound/microbubble therapy, but also reveals the mechanism of ultrasound/immunoliposome microbubbles drug delivery system mediated BBB disrupted, particularly the receptor-mediated transcellular pathway. The study will provide new evidences to ultrasound

英文关键词： Blood-Brain barrier；Ultrasound combined with nanoparticle；Glioma；Transferrin；drug delivery system