炎症因子诱导的动脉粥样硬化斑块靶向的细胞递药系统研究

项目名称： 炎症因子诱导的动脉粥样硬化斑块靶向的细胞递药系统研究

项目编号： No.81503006

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 苏志桂

作者单位： 中国药科大学

项目金额： 17.9万元

中文摘要： 动脉粥样硬化（AS）是心脑血管疾病发生的主要病理基础，AS的发生和发展始终伴随着炎症反应。动脉血管壁的炎性反应是AS斑块形成的重要诱因，斑块的破裂和脱落导致血栓的形成，危及生命。利用药物阻止斑块内炎症进展和稳定斑块具有重要的临床治疗意义。药物对炎性斑块的作用呈剂量依赖性，但药物进入斑块内的浓度很低。本项目根据AS斑块的炎性特征和病理结构，将具抗炎、稳定斑块的辛伐他汀通过中性粒细胞作为载体在炎症因子的引导靶向下穿透进入炎性斑块内部，提高药物在斑块内的浓度。本项目通过构建荷载辛伐他汀的中性粒细胞传递系统和AS动物模型，研究细胞递药系统的稳定性、对斑块炎症信号的引导性靶向和穿透性等，探讨细胞递送药物治疗的可行性和有效性，揭示通过生理病理因子间相互作用实现药物诱导递送的机制等。本项目的研究为AS的治疗提供创新高效的药物载体平台，对探索药物对AS斑块的作用及机制，推动抗AS药物的发展具有重要价值。

中文关键词： 动脉粥样硬化；斑块；炎症因子；细胞载体；靶向

英文摘要： Atherosclerosis(AS) is the major pathological basis of cardiovascular and cerebrovascular diseases. The occurrence and development of AS is accompanied by inflammation process. This inflammation reaction inside arterial wall plays an important role in forming atherosclerotic plaque, thinning the inflamed caps and triggering the plaque rupture, which will lead to the occurrence of thrombus and threat to life. Therefore, impairing inflammation and enhancing the stability of plaque by drugs with anti-inflammation activity have important clinical significance. Recent researches have demonstrated that the effect of anti-inflammation agent for preventing inflammation in plaque presents dose-dependent, however, via traditional administration only little part of drug will accumulate in plaque. Thus, according to the pathogenesis, inflammation, pathogenic structure and microenvironment of AS, a novel atherosclerotic plaque-targeting delivery system is developed based on neutrophils carrier for simvastatin-loaded lipid nanoparticls. Guided by the inflammatory signal gradient, these simvastatin-loaded neutrophils will be recruited to the inflammatory site, penetrate the wall of vascular endothelial cell and enhance the accumulation of simvastatin into atherosclerotic plaque. For proof of neutrophils as a feasible, efficient and safe drug targeting carrier, as well as illustration of the target mechanism based on interaction between physiological and pathological factors, numerous researches are being performed including the stability of neutrophils loading simvastatin-encapsulated lipid nanoparticles, physiological activity, inflammatory signal tropism and vascular penetration effect. This design of such neutrophils self-targeting carrier provide an innovative and efficient platform for treatment of AS, which will aid in exploration of the effect and mechanism of drugs on the AS plaque and promote the development of anti-AS drug.

英文关键词： Atherosclerosis;Plaque;Inflammatory cytokine;Cell carrier;Target