Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system

Male Benzylamines Mice, Inbred ICR 0303 health sciences Brain Endothelial Cells Article Brain Ischemia Polyethylene Glycols 3. Good health Rats, Sprague-Dawley Aminosalicylic Acids 03 medical and health sciences Drug Delivery Systems Neuroprotective Agents Microscopy, Electron, Transmission Microscopy, Fluorescence Blood-Brain Barrier Liposomes Animals Amino Acid Sequence Particle Size Peptides Cells, Cultured
DOI: 10.1038/srep12651 Publication Date: 2015-07-29T10:02:10Z
ABSTRACT
AbstractThe 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.
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