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目的构建angiopep-2与转铁蛋白共修饰脂质体,并对其跨血脑屏障能力进行评价。方法制备angiopep-2与转铁蛋白(TF)共修饰脂质体(ANG/TF-LPs),考察其粒径、Zeta电位和血清稳定性等理化特征。通过定量细胞摄取实验考察脑内皮bEnd.3细胞对ANG/TF-LPs的摄取效率。构建血脑屏障体外模型,考察不同脂质体的跨血脑屏障能力。结果所制备的ANG/TF-LPs粒径为(93.2±13.5)nm,Zeta电位为(7.55±1.85)mV,且在24h内具有良好的血清稳定性。体外细胞摄取实验表明,bEnd.3细胞对ANG/TF-LPs的摄取效率分别是TF-LPs、ANG-LPs和LPs的2.9倍、2.4倍和4.8倍,差异具有统计学意义(P<0.01);ANG/TF-LPs的跨血脑屏障效率分别是TF-LPs、ANG-LPs和LPs的3.1倍、2.9倍和5.4倍,差异具有统计学意义(P<0.01)。结论 ANG/TF-LPs制备工艺简单,经过angiopep-2与转铁蛋白修饰后,脂质体的跨血脑屏障能力显著增强,是一种潜在高效的脑部靶向给药系统。
Objective To construct liposome co-modified with angiopep-2 and transferrin and evaluate its ability to cross the blood-brain barrier. Methods Angiopep-2 and transferrin (TF) co-modified liposomes (ANG / TF-LPs) were prepared and their physical and chemical characteristics such as particle size, Zeta potential and serum stability were investigated. The uptake efficiency of ANG / TF-LPs by bEnd.3 cells in brain endothelium was investigated by quantitative cellular uptake assay. The in vitro model of blood-brain barrier was constructed to investigate the ability of different liposomes to cross the blood-brain barrier. Results The particle size of ANG / TF-LPs was (93.2 ± 13.5) nm and the Zeta potential was (7.55 ± 1.85) mV, and the serum stability of ANG / TF-LPs was good within 24 hours. In vitro cell uptake experiments showed that uptake efficiency of ANG / TF-LPs by bEnd.3 cells was 2.9-fold, 2.4-fold and 4.8-fold higher than that of TF-LPs, ANG-LPs and LPs respectively (P <0.01) The trans-BBB efficiencies of ANG / TF-LPs were 3.1-fold, 2.9-fold and 5.4-fold higher than those of TF-LPs, ANG-LPs and LPs, respectively, with statistical significance (P <0.01). Conclusion The preparation of ANG / TF-LPs is simple. After angiopep-2 and transferrin are modified, liposomal trans-blood-brain barrier function is significantly enhanced. It is a potential and efficient brain targeting delivery system.