长循环超顺磁性氧化铁脂质体纳米微粒的制备及理化性质

摘要

BACKGROUND: Common superparamagnetic iron oxide nanoparticles (SPIO) have limitations to apply to the reticuloendothelial system (RES) rather than non-RES.OBJECTIVE: To study the preparation and physico-chemical property of long-circulating SPIO liposome nanoparticles as novel MR contrast agent.METHODS: The long-circulating SPIO liposome nanoparticles were prepared by three steps: ①preparation of long-circulating blank liposomes by film dispersion method, using DSPG and DSPE-PEG2000 with a molar ratio of 20 : 1; ②synthesis of lauric acid-stabilized SPIO nanoparticles; ③the two products above were dialyzed for 3 days. Then, physico-chemical property of long-circulating SPIO liposome nanooparticles was measured.RESULTS AND CONCLUSION:①?Laurie acid-stabilized SPIO nanoparticles, long-circulating blank liposomes and long-circulating SPIO liposomes appeared as circular particles with uniform size approximately 12 nm, 20 nm, 60 nm, respectively in the electron microscope. ②XRD analysis of SPIO nanoparticles: lauric acid-stabilized SPIO nanoparticles and long-circulating SPIO liposomes nanoparticles were face-centered cubic spinel structure of Fe3O4, and the crystalline particles were in good form. ③With the Malvern-3000HS, the measurements of long-circulating SPO liposomes were: di = 78.7 nm, peak area: 100%, peak number 1, dv = 76.7 nm, peak area: 100%, peak number 1, dn = 73.5 nm, peak area: 100%, peak number 1, polydispersity coefficient: 0.212. ④Standard curve of iron: A=0.194 7C+0.000 8, R2=0.998 2. The Fe concentration of long-circulating SPIO liposome was 6.721 3 g/L. ⑤As the iron concentration increases, T2 values of long-circulating SPIO liposome gradually decreased. Long-circulating SPIO liposomes were prepared with suitable sizes and distribution, and could be made into contrast agent for subcutaneous or intravenous injection.%背景 常见的超顺磁性氧化铁纳米微粒都局限应用于网状内皮系统病变的诊断.目的 尝试制备新型MR 对比剂长循环超顺磁性氧化铁纳米微粒脂质体纳米微粒,并对其理化性质进行测定.方法 采用以下方法制备长循环超顺磁性氧化铁脂质体纳米微粒:①精密称取一定量DSPG、DSPE-PEG2000,采用薄膜分散法合成长循环空白脂质体纳米微粒.②采用化学共沉淀法,在碱性条件下与月桂酸反应形成月桂酸稳定的超顺磁性氧化铁纳米微粒.③将上述反应产物以一定比例混合,加入TES 缓冲液透析3 d,过凝胶柱去除过大的脂质体及游离的磷脂.结果 与结论 长循环超顺磁性氧化铁脂质体在电镜下显示为类圆形、大小较均匀.衍射图说明产物均为面心立方尖晶石结构的Fe3O4,而且粒子的结晶状态很好.多分散系数为0.212.长循环超顺磁性氧化铁脂质体纳米微粒铁含量为6.721 3 g/L.长循环超顺磁性氧化铁脂质体T2 值随着铁浓度的增加逐渐下降.提示制备的长循环超顺磁性氧化铁脂质体纳米微粒粒径大小适宜,分布均匀,可制成适合于皮下或静脉注射的制剂.