Abstract

Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer’s disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.

摘要

Osthole (Ost) 是一种香豆素化合物，是治疗阿尔茨海默病 (AD) 的潜在药物。然而，Ost 的有效性受到溶解度、生物利用度和血脑屏障低渗透性的限制。在本研究中，我们构建了表面修饰 CXCR4 的 Ost 脂质体（CXCR4-Ost-Lips），并研究了脂质体在 APP-SH-SY5Y 细胞中的细胞内分布。此外，CXCR4-Ost-Lips 的神经保护作用在体外和体内进行了检查。结果表明CXCR4-Ost-Lips增加了APP-SH-SY5Y细胞的细胞内摄取并发挥了体外细胞保护作用. Ost脑分布结果显示CXCR4-Ost-Lips延长了小鼠的周期时间，增加了Ost在脑内的积累。此外，CXCR4-Ost-Lips 增强了 Ost 在缓解 AD 相关病理方面的作用。这些结果表明 CXCR4 修饰的脂质体是治疗 AD 的潜在 Ost 载体。