title: Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system.
abstract: The treatment for ischemic stroke is one of the most challenging problems and the therapeutic effect remains unsatisfied due to the poor permeation of drugs across the blood brain barrier (BBB). In this study, HAIYPRH (T7), a peptide that targeted to transferrin receptor (TfR) can mediate the transport of nanocarriers across the BBB, was conjugated to liposomes for ischemic stroke targeting treatment of a novel neuroprotectant (ZL006). T7-conjugated PEGylated liposomes (T7-P-LPs) loaded with ZL006 (T7-P-LPs/ZL006) were showed satisfactory vesicle size and size distribution. Furthermore, the cellular uptake results showed that T7 modification increased liposomes uptake by the brain capillary endothelial cells (BCECs) and little cytotoxicity of liposomes with or without ZL006 was observed. The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB. The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006. T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects. They could be used as a potential targeted drug delivery system of ischemic stroke treatment.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
mesh_terms: D000595:Amino Acid Sequence; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000648:ultrastructure; D008297:Male; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D014018:Tissue Distribution
chemical_list: D000636:Aminosalicylic Acids; D001596:Benzylamines; D008081:Liposomes; D018696:Neuroprotective Agents; D010455:Peptides; C000607694:ZL006 compound; D011092:Polyethylene Glycols