神经生长因子脂质体跨血脑屏障体内外研究

Study on nerve growth factor liposomes on crossing blood-brain barrier in vitro and in vivo

目的 研究神经生长因子 (nervegrowthfactor,NGF)脂质体在体外血脑屏障 (blood brainbarrier,BBB)模型上的通透性以及在体内脑组织的分布 ,并对体内外结果进行相关性分析。方法 用小鼠脑微血管内皮细胞 (BMVEC)建立的BBB体外实验模型 ,研究NGF脂质体在体外模型上的通透率 ;1 2 5I NGF和SDS PAGE法联合使用研究NGF脂质体在脑组织的分布。结果 NGF脂质体的最高包封率为 34% ,平均粒径小于 10 0nm。脂质体能够增加NGF在BBB模型上的通透率 ,以NGF SSL T为最大。脑组织药物浓度次序为NGF SSL T >NGF SSL +RMP 7>NGF SSL。体内外结果具有良好相关性。结论 脂质体能够增加NGF跨越BBB的能力 ,RMP 7偶联在脂质体上 (NGF SSL T)效果好于RMP 7与脂质体的简单混合 (NGF SSL +RMP 7)。

Aim To study the permeability of nerve growth factor (NGF) liposomes (NGF-L, NGF-SSL, NGF-SSL-T) on the blood-brain barrier (BBB) model and the distribution in vivo, and analyze the correlation between the results in vitro and in vivo. Methods The BBB model in vitro was established by using mouse brain microvascullar endothelial cell, and the model was applied to study the permeability of NGF liposomes. The distribution of NGF of each group was studied by 125I labeled and SDS-PAGE method. Results The highest encapsulation proportion was 34%, and the mean size of NGF liposomes was below 100 nm. The permeability of NGF liposomes on in vitro BBB model showed that the liposome could promote NGF to transport across the BBB, the permeability of NGF-SSL-T was the highest. The distribution in the brain showed in an order of NGF concentration NGF-SSL-T > NGF-SSL+RMP-7 > NGF-SSL > NGF-L. There was a close relationship between P e (permeability coefficient on in vitro BBB model) and BUI (brain uptake constant in vivo). Conclusion Liposomes can promote NGF to transport across the BBB, and the transporting ability BBB of NGF-SSL-T which RMP-7 incorporated into the surface of NGF liposomes is the best.