C3F8脂质体超声微泡造影剂制备的初步研究

目的:制备稳定的脂质体C3F8气体微泡,为深入研究sulfatide导向的靶向声学造影剂准备必要材料.方法:通过改变卵磷脂、胆固醇和硬脂酸的比例及水化液成分,采用薄膜水化法,分多组实验,探索制备脂质体C3F8气体微泡的条件,观察和记录其物理特性参数.结果:质量比为3/1/(0.2-0.4)的卵磷脂/胆固醇/硬脂酸混合物的乙醚溶液,在压力-0.030MPa至-0.035MPa、转速130 r/min、37℃水浴加热的条件下旋蒸35 min左右制膜,然后用20％葡萄糖PBS进行水化,充入C3F8气体,50℃水浴70 min和超声30 s的条件下,所制备的微泡大小在2-4μm,平均半衰期为119 min,表面带有更多的负电荷(平均电势-7.12).结论:在该条件下制备的脂质体C3F8气体微泡造影剂的形态相对规则、粒径均一、稳定性好,符合通过肺循环的条件要求,下一步可以在此基础上进行导向分子的偶联研究.

Preparation of C3F8 Liposome Ultrasonic Contrast Agents

Objective: To prepare stable liposome microbubbles containing C3F8 for preparing a new type of sulfatide-guided ultrasound contrast agents that would be useful in echocardiography.Methods: The stable liposome microbubbles containing C3F8 were prepared by optimizing the experimental conditions such as the composition of liposomal raw materials,solution type for rehydration,vibrating time by ultrasound and the gas composition.The prepared liposome microbubbles are characterized by measuring the concentration,surface potential,size and size distribution.Microbubbles with diameters of 2-4 μm and half-life of more than 30 min were prepared using a formula of lecithin/cholesterol/stearic acid = 3/1/(0.2-0.4).The preparation conditions were optimized as follows.First,a membrane was prepared by rotaevaporation for 35 min at a spin speed of 130 r/min under a pressure between-0.030 MPa to-0.035 MPa.Then,the membrane was hydrated with PBS solution containing 20% glucose in an atmosphere of C3F8 gas at 50 ℃.Results: The resulted microbubbles have moderate diameters of 2-4 μm and are negatively charged.In vitro ultrasound scanning experiments showed that the microbubbles can enhance the contrast effectively.Conclusion: We have successively prepared microbubbles with a suitable size and size distribution,and good in vitro stability.The microbubbles showed effective contrast enhancing in vitro ultrasound imaging.Then sulfatide molecules will be coupled to the microbubbles as a targeting agent.