Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system.
Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system.
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DOI：
10.1038/srep12651
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发表时间：
2015-07-29
影响因子：
4.6
通讯作者：
Xin H
中科院分区：
文献类型：
--
作者：
Wang Z;Zhao Y;Jiang Y;Lv W;Wu L;Wang B;Lv L;Xu Q;Xin H
缺血性脑卒中的治疗是最具挑战性的问题之一，由于药物穿过血脑屏障（BBB）的渗透性差，治疗效果仍不理想。在这项研究中，HAIYPRH (T7) 是一种靶向转铁蛋白受体 (TfR) 的肽，可以介导纳米载体跨 BBB 的运输，它与脂质体缀合，用于靶向治疗新型神经保护剂 (ZL006) 的缺血性中风。负载 ZL006 的 T7 缀合聚乙二醇化脂质体 (T7-P-LPs) (T7-P-LPs/ZL006) 显示出令人满意的囊泡尺寸和尺寸分布。此外，细胞摄取结果表明，T7修饰增加了脑毛细血管内皮细胞（BCEC）对脂质体的摄取，并且观察到有或没有ZL006的脂质体几乎没有细胞毒性。体内生物分布和近红外荧光成像证明T7修饰使脂质体显着增强了脂质体穿过血脑屏障的转运。药效学研究表明，与未修饰的脂质体或游离 ZL006 相比，T7-P-LPs/ZL006 表现出减少的梗塞体积和改善的神经功能缺损。 T7-P-LPs/ZL006可以靶向大脑并表现出显着的神经保护作用。它们可以用作缺血性中风治疗的潜在靶向药物递送系统。
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.