Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery
Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery
复制标题
采用 TAT 修饰胆固醇配制的脂质体，可增强大脑输送
DOI：
10.1016/j.ijpharm.2011.07.021
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发表时间：
2011-10-31
影响因子：
5.8
通讯作者：
He, Qin
中科院分区：
文献类型：
--
作者：
Qin, Yao;Chen, Huali;He, Qin
由于血脑屏障（BBB）的存在，药物向脑的递送是一个主要挑战。细胞穿透肽达特似乎可以迅速进入细胞，可以有效地穿过血脑屏障。考虑到这一点，开发了一种新的TAT修饰的脂质体（TAT-LIP），用于克服正常药物制剂向大脑的无效递送。靶向脂质体制剂总是由作为锚的改性磷脂组成。然而，胆固醇，另一种脂质体组分，更稳定和更便宜，尚未被充分研究作为替代锚。本研究将达特与胆固醇共价结合制备脂质体。本实验观察了大鼠脑毛细血管内皮细胞（BCECs）对TAT-LIP的摄取，并探讨了TAT-LIP途径的内吞机制。建立体外血脑屏障模型，研究其跨血脑屏障的能力及其转运机制。进一步鉴定了每种制剂的生物分布。结果表明，TAT-LIP的正电荷在促进其脑内释放方面起着重要作用。吸收性内吞作用可能是TAT-LIP通过血脑屏障的机制之一。总之，体外和体内实验数据表明，TAT-LIP是一种很有前途的脑药物传递系统，由于其高的跨血脑屏障的传递效率。(C)2011爱思唯尔有限公司版权所有。
Delivery of drugs to the brain is a major challenge due to the presence of the blood-brain barrier (BBB). The cell penetrating peptide TAT, which appears to enter cells with alacrity, can pass through the BBB efficiently. With this in mind, a novel TAT-modified liposome (TAT-LIP) was developed for overcoming the ineffective delivery of normal drug formulation to the brain. Targeting liposomal formulations are always composed of modified phospholipids as an anchor. However, cholesterol, another liposomal component, which was more stable and cheaper, has not been fully investigated as an alternative anchor. In this study, TAT was covalently conjugated with the cholesterol to prepare the liposome. The cellular uptake by brain capillary endothelial cells (BCECs) of rats and the mechanism of TAT-LIP pathway of endocytosis was explored. The blood brain barrier model in vitro was established to evaluate the transendothelial ability crossing the BBB and its transport mechanism. The biodistribution of each formulation was further identified. The results showed that the positive charge of the TAT-LIP played an important role in enhancing its brain delivery. The absorptive endocytosis might be one of the mechanisms of TAT-LIP crossing the BBB. In conclusion, the experimental data in vitro and in vivo indicated that the TAT-LIP was a promising brain drug delivery system due to its high delivery efficiency across the BBB. (C) 2011 Elsevier B.V. All rights reserved.