Background

The difficulty of drugs to cross the blood-brain barrier (BBB) to reach specific sites and target multiple factors responsible for neurovegetative diseases necessitates the development of an effective drug delivery system.

Methods

Rabies virus glycoprotein (RVG)- and transferrin (Tf)-grafted liposomes were constructed to deliver epigallocatechin gallate (EGCG) and FK506 to BBB against neurodegeneration for Parkinson's disease (PD) treatment.

Significant findings

Surface RVG and Tf revealed substantial improvement in BBB permeability of EGCG and FK506, and incorporation of phosphatidy-l-serine (PS) in RVG-Tf-EGCG-FK506-liposomes ameliorated α-synuclein docking. EGCG and FK506-encapsulated liposomes decreased cytotoxicity to 1-methyl-4-phenylpyridinium-impacted neurons. Immunofluorescence and western blot studies demonstrated better activity of RVG-Tf-EGCG-FK506-PS-liposomes in suppressing Bax, α-synuclein, caspase-3, p-tau protein, p-p38, p-ERK1/2 and p-cJNK expressions, and in increasing Bcl-2, tyrosine hydroxylase, dopamine transporter, p-CREB and p-ERK5 expressions. Multi-targeted RVG-Tf-PS-liposomes advantaged BBB permeation and contributed to neuroprotective effect to promote the efficiency of EGCG and FK506 in PD management.

中文翻译：

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狂犬病病毒糖蛋白和转铁蛋白功能化脂质体提高表没食子儿茶素没食子酸酯和 FK506 活性并介导 MAPK 对抗帕金森病神经元凋亡

背景

药物难以穿过血脑屏障 (BBB) 到达特定部位并靶向导致神经植物疾病的多种因素，因此需要开发有效的药物输送系统。

方法

狂犬病病毒糖蛋白 (RVG) 和转铁蛋白 (Tf) 移植脂质体被构建用于将表没食子儿茶素没食子酸酯 (EGCG) 和 FK506 递送至 BBB，以对抗帕金森病 (PD) 治疗的神经变性。

重要发现

表面 RVG 和 Tf 显示 EGCG 和 FK506 的 BBB 通透性显着改善，并且在 RVG-Tf-EGCG-FK506-脂质体中掺入磷脂酰-l-丝氨酸 (PS) 改善了 α-突触核蛋白对接。EGCG 和 FK506 封装的脂质体降低了对 1-甲基-4-苯基吡啶鎓影响的神经元的细胞毒性。免疫荧光和蛋白质印迹研究表明 RVG-Tf-EGCG-FK506-PS-脂质体在抑制 Bax、α-突触核蛋白、caspase-3、p-tau 蛋白、p-p38、p-ERK1/2 和 p-cJNK 方面具有更好的活性表达，并增加 Bcl-2、酪氨酸羟化酶、多巴胺转运蛋白、p-CREB ​​和 p-ERK5 的表达。多靶点 RVG-Tf-PS-脂质体有利于 BBB 渗透并有助于神经保护作用，从而提高 EGCG 和 FK506 在 PD 管理中的效率。