贾喜乐,吕辉,宋益民
JIA Xi-le,LV Hui,SONG Yi-min

• 1:青岛科技大学制药工程系
• 2:青岛市中心医院神经内科

摘要(Abstract)：

目的制备了乙酰水杨酸/氨基多糖(acetylsalicylic acid/amino polysaccharide,ASA/APS)纳米粒,研究了不同反应条件对纳米粒子载药量和接枝率的影响,初步探讨了其抗血栓作用及其机制。方法以氨基多糖为载体材料,乙酰水杨酸为模型药物采用大分子复合法制备氨基多糖载药纳米粒,以红外线光谱(fourier transform infrared spectroscopy,FT-IR)、扫描电子显微镜(scanning electron microscope,SEM)对其结构进行表征,激光衍射法测定纳米粒子粒径及分布,电刺激法观察其对血栓形成的影响。结果乙酰水杨酸成功接枝到氨基多糖表面,且形成的纳米粒呈近球形,平均粒径为(79.3±24.6)nm,分布范围较小,呈正态分布。氨基多糖分子质量、反应温度、pH值、n(ASA):n(APS)是影响药物载药量和接枝率的主要因素。在pH 7.4下,ASA易从ASA/APS纳米粒中释放,且能明显延长颈动脉血流阻塞时间(occlusion time,OT)。结论氨基多糖分子质量为32×10~4u、反应温度为55~60℃、pH=5、反应物量比n(ASA):n(APS)=0.75:1.00条件下制得的ASA/APS纳米粒子的接枝率、载药量最高,在偏碱性条件下ASA易从ASA/APS纳米粒中释放,且具有明显的抗血栓形成作用。
Objective To prepare acetyl salicylic acid/amino polysaccharide(ASA/APS) nanoparticles.Meanwhile,to investigate the influence of different reaction conditions on drug-loading rate and grafting ratio.Furthermore,to preliminarily explore the antithrombosis effect and mechanism of ASA/APS nanoparticles.Methods The drug-loaded amino polysaccharide nanoparticles were prepared with acetylsalicylic acid as model drug and amino polysaccharide as the carrier material through macromolecule compound method.Infrared spectroscopy(FT-IR) and scanning electron microscope(SEM) were used for the characterization of ASA/APS nanoparticles,laser diffraction method was used for the determination of particle size and distribution of nanoparticles,and electrical stimulation was used for the observation of its effects on thrombosis in rat.Results Acetylsalicylic acid was successfully grafted to amino polysaccharide.The formed nanoparticles were nearly spherical in shape,and there was a normal distribution of nanoparticles diameter with small distribution range and the average particle size was(79.3 ±24.6) nm.Amino molecular weight,reaction temperature pH,n(ASA):n(APS) molar ratio were major factors impacting drug-loading rate and grafting ratio.ASA easily released from the formed ASA/APS nanoparticles in pH 7.4.Appropriate concentration of acetyl salicylic acid/amino polysaccharide nanoparticles obviously extended the occlusion time(OT).Conclusions Under the condition that amino polysaccharide molecular weight was 32 ×10~4u,reaction temperature was 55-60℃,pH was 5 and molar ratio of n(ASA):n(APS) was 0.75:1.00,grafting ratio and drug-loading rate of ASA/APS nanoparticles reached maximum.ASA easily released from the formed ASA/APS nanoparticles,which had obvious antithrombosis effect,in subalkaline cindition.

关键词(KeyWords)： 乙酰水杨酸;氨基多糖;大分子复合法;纳米粒;抗血栓
acetyl salicylic acid;amino polysaccharide;macromolecular compound method;nanoparticle;antithrombosis

Abstract:

Keywords:

基金项目(Foundation): 山东省科技发展计划项目(2012GNC11307);; 青岛市民生科技计划项目(14-2-3-2-nsh)

作者(Author): 贾喜乐,吕辉,宋益民
JIA Xi-le,LV Hui,SONG Yi-min

DOI: 10.14066/j.cnki.cn21-1349/r.2017.03.002

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