Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery

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.