title: Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals.
abstract: The treatment of central nervous system diseases such as brain glioma is a major challenge due to the presence of the blood-brain barrier (BBB). A cell-penetrating peptide TAT (AYGRKKRRQRRR), which appears to enter cells with alacrity, was employed to enhance the delivery efficiency of normal drug formulation to the brain. Targeting liposomal formulations often apply modified phospholipids as anchors. However, cholesterol, another liposomal component more stable and cheaper, has not been fully investigated as an alternative anchor. In our study, TAT was covalently conjugated with cholesterol for preparing doxorubicin-loaded liposome for brain glioma therapy. Cellular uptake by brain capillary endothelial cells (BCECs) and C6 glioma cells was explored. The anti-proliferative activity against C6s confirmed strong inhibitory effect of the liposomes modified with doxorubicin-loaded TAT. The bio-distribution findings in brains and hearts were evident of higher efficiency of brain delivery and lower cardiotoxic risk. The results on survival of the brain glioma-bearing animals indicate that survival time of the glioma-bearing rats treated with TAT-modified liposome was much longer than in the other groups. In conclusion, the potency of the TAT-modified liposome to enter the BBB appears to be related with the TAT on the liposome's surface. The TAT-modified liposome may improve the therapeutic efficacy on brain glioma in vitro and in vivo.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Sichuan University, #17 Section 3, Renmin Nan Road, Chengdu Municipality 610041, Sichuan Province, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qin
authors.forename: Huali
authors.initials: H
authors.lastname: Chen
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.forename: Wenmin
authors.initials: W
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Kuai
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D042783:Endothelial Cells / Q000378:metabolism; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005910:Glioma / Q000188:drug therapy*; D008081:Liposomes; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D015696:Gene Products, tat; D008081:Liposomes; D004317:Doxorubicin; D002784:Cholesterol