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
AUTHORS (9)
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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