超顺磁性四氧化三铁长循环脂质体的制备及表征

目的：构建磁共振对比剂超顺磁性四氧化三铁长循环脂质体（PS），并对其理化性质与稳定性进行初步评价。方法：采用化学共沉淀法合成柠檬酸修饰的超顺磁性四氧化三铁纳米粒，并用脂质材料将纳米粒外层包被，制备得PS。采用透射电镜、动态光散射、凝胶色谱及磁共振成像等，对PS的形态、粒径、Zeta电位、包封率及弛豫率进行评价，并考察PS在4 ℃条件下的稳定性。结果：制备的PS为圆形或类圆形粒子，粒径为（141±1）nm，PDI为0.242±0.006，Zeta电位为（-17.8±1.0）mV，包封率为（91.73±5.18）%。体外MR成像结果表明，PS的弛豫率为355.20 mM^-1·s^-1。稳定性试验结果表明，PS在4 ℃条件下贮藏10 d，其粒径 [（151±3.2）nm]、PDI（0.273±0.012）、Zeta电位[（-19.9±0.3）mV]和包封率[（93.05±6.52）%]，均无显著性变化。结论：本研究成功制备了超顺磁性四氧化三铁长循环脂质体MR对比剂，为进一步构建MR可视化肿瘤靶向药物传递系统提供了有效的物质基础。

Preparation and characterization of superparamagnetic iron oxide loaded of PEGylated liposomes

OBJECTIVE To construct a MR contrast agent -superparamagnetic iron oxide long-circulating liposome (PS) and evaluate its physical and chemical properties and stability. METHODS Citric acid modified superparamagnetic iron oxide nanoparticles (CA-SPIONs) were synthesized by chemical coprecipitation method. Then, CA-SPIONs were encapsulated by PEGylated liposomes via the thin film method and peglipid post insertion. Transmission electron microscopy (TEM), dynamic light scattering (DLS), gel chromatography and magnetic resonance (MR) imaging were used to characterize the morphology, particle size, Zeta potential, encapsulation efficiency and relaxation rate of PS. The stability of PS at 4℃ was also evaluated. RESULTS The prepared PS system was showed spherical or oval vesicles in mean particle size of (141±1) nm, and the PDI was 0.242±0.006, and Zeta potential was (-17.8±1.0) mV, and the encapsulation efficiency was (91.73±5.18)%. In vitro MR imaging showed that the relaxation rate of PS was 355.20 mM^-1·s^-1. The stability test showed that there were no significant changes in particle size[(151±3.2) nm], PDI (0.273±0.012), zeta potential[(-19.9±0.3) mV], and entrapment efficiency[(93.05±6.52)%] of PS stored at 4 oC for 10 days. CONCLUSION The superparamagnetic iron oxide long-circulating liposomal MR contrast agent was successfully prepared in this study, which provides an effective material basis for the further construction of MR visualization tumor-targeting drug delivery system.