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The two stretch bands are characteristic absorption of the secondary amide groups in the structure of Mal-PEG-DSPE. The spectrum of Mal-PEG-DSPE showed a weak C=O stretch band at 1686.21 cm −1 and a broad N-H stretch band at 3600–3200 cm −1, centered at 3403.63 cm −1.
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The FTIR spectra of Mal-PEG-DSPE and T7-PEG-DSPE are shown in Fig. Finally, the in vivo anti-ischemic stroke efficacy of T7-P-LPs/ZL006 was evaluated through rats middle cerebral artery occlusion (MCAO) model. Secondly, the in vitro and in vivo targeting efficacy of T7-P-LPs were studied via cellular and animals model. Firstly, T7 was conjugated to liposomes and the morphology, particle size, encapsulation efficiency and loading capacity were investigated. With these considerations, we developed T7 peptide modified ZL006 loading liposome (T7-P-LPs/ZL006) to improve the drug delivery to brain and enhance the therapeutic effect against ischemic stroke for ZL006 in this study. However, there is no previous study about T7-modified liposomes (T7-P-LPs) utilization on targeted therapy of ischemic stroke through TfR-mediated endocytosis. Through the T7 peptide modification, nanocarriers could effectively achieve the active targeting to brain site. Moreover, T7-conjugated polyamidoamine dendrimer was used for nanoscale brain-targeted magnetic resonance imaging 11. Recently, T7-modified nanoparticles were reported with good targeting ability to brain tumors 9, 10. A special ligand peptide of TfR, HAIYPRH (T7), can specially bind to TfR and mediate the transport of nanocarriers across the BBB 7, 8. It is over-expressed on the brain capillaries endothelial cells, which makes TfR an attractive target. As known, transferrin receptor (TfR) can mediate the transcytosis of transferrin-bound iron. Receptor-mediated endocytosis is one of the most important mechanisms of brain targeting drug delivery system. To solve the poor penetration across BBB, many strategies have been developed these years. Consequently, there is an increasing need for novel method to overcome the BBB for the central nervous system diseases treatment. Although there is a compromised endothelial barrier which facilitates molecular transport under some disease conditions such as Alzheimer’s disease and ischemic stroke, BBB is still present in the infiltrating margin of brain diseases 6. Even so, the available therapeutics has less than optimal usefulness for ischemic stroke, mainly owing to the low permeability across the blood brain barrier (BBB). Moreover, ZL006 has no effect on aggressive behavior and spatial memory. It could selectively block the coupling of neuronal nitric oxide synthase and the scaffold protein postsynaptic density 95 kDa and had potent neuroprotective activity. ZL006, 5-(3, 5-dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid, was a special uncoupling agent of ischemia-induced reactions screened by our center 5. Obviously there is an urgent need for an effective treatment for ischemic stroke.īecause of poor tolerance for humans, many drugs have been failed to gain approval for clinical use to treat ischemic stroke 4. The sudden onset leaves the individual and the family ill-prepared to deal with their residual impairments of physical, psychological and social functions 1, 2, 3. The impact of stroke, particularly ischemic stroke, can be devastating and unlike other disabling neurological diseases, stroke has a high incidence, prevalence and rate of subsequent disability. They could be used as a potential targeted drug delivery system of ischemic stroke treatment. T7-P-LPs/ZL006 could be targeted to brain and displayed remarkable neuroprotective effects.
Peptide for anti stroke free#
The pharmacodynamic study suggested that, T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological deficit compared with unmodified liposomes or free ZL006. The in vivo biodistribution and near-infrared fluorescence imaging evidenced that T7 modification rendered liposomes significantly enhanced the transport of liposomes across the BBB. 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. T7-conjugated PEGylated liposomes (T7-P-LPs) loaded with ZL006 (T7-P-LPs/ZL006) were showed satisfactory vesicle size and size distribution. 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). 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).