title: Comparison of four different peptides to enhance accumulation of liposomes into the brain.
abstract: The cell penetrating peptide TAT, which appears to enter cells with alacrity, can pass through the BBB efficiently. It has been indentified to enhance the brain delivery of the liposome. However, little was known about its mechanism. TAT contains a basic region consisting of six arginine and two lysine residues. These eight basic amino acids seem to be the key to its highly efficient membrane translocation and brain delivery. In this study, four selected peptides are synthesized. (1) TAT peptide with terminal Cysteine (Cys-AYGRKKRRQRRR). (2) TAT peptide with disordered sequence (Cys-RKARYRGRKRQR). (3) Glycine and glutamic acid substituted TAT peptide (Cys-AYGGQQGGQGGG). (4) R8 (Cys-RRRRRRRR). Liposomes were chosen as the delivery vehicle. The peptide was covalently bonded with the liposome. We compare four peptides for their brain targeting potential, and investigate their ability to target liposomes to the brain in vitro and in vivo. The cellular uptake of these four liposomes by brain capillary endothelial cells (BCECs) of rats and C6s and the mechanism of the pathway of endocytosis were explored. Biodistribution in vivo was also investigated qualitatively and quantitatively. The results showed that the charge of the peptide played an important role in enhancing its brain delivery. The sequence had little to do with its membrane translocation and brain delivery indicated there might be no specific receptor or transporter for the Tat peptide.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qin
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Huali
authors.initials: H
authors.lastname: Chen
authors.forename: Wenmin
authors.initials: W
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Kuai
authors.forename: Fulan
authors.initials: F
authors.lastname: Xie
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D004705:Endocytosis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008081:Liposomes; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D014018:Tissue Distribution; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007202:Indicators and Reagents; D008081:Liposomes; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C520542:tat peptide (48-57), Human immunodeficiency virus 1