Andrade Stéphanie, Pereira Maria C, Loureiro Joana A
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Colloids Surf B Biointerfaces. 2023 May;225:113270. doi: 10.1016/j.colsurfb.2023.113270. Epub 2023 Mar 17.
Alzheimer's disease (AD) is an incurable neurological illness and the leading cause of dementia, characterized by amyloid β (Aβ) fibril deposits. Caffeic acid (CA) has demonstrated potential value for AD therapy due to its anti-amyloidogenic, anti-inflammatory, and antioxidant properties. However, its chemical instability and limited bioavailability limit its therapeutic potential in vivo. Herein, liposomes loading CA were produced by distinct techniques. Taking advantage of the overexpression of transferrin (Tf) receptors in brain endothelial cells, Tf was conjugated to the liposomes' surface to direct the CA-loaded nanoparticles (NPs) to the blood-brain barrier (BBB). The optimized Tf-modified NPs exhibited a mean size of around 140 nm, a polydispersity index lower than 0.2, and a neutral surface charge, being appropriate for drug delivery. The Tf-functionalized liposomes showed suitable encapsulation efficiency and physical stability for at least 2 months. Furthermore, in simulated physiological settings, the NPs ensured the sustained release of CA for 8 days. The anti-amyloidogenic efficacy of the optimized drug delivery system (DDS) was investigated. The data show that CA-loaded Tf-functionalized liposomes are capable of preventing Aβ aggregation and fibril formation, and disaggregating mature fibrils. Hence, the proposed brain-targeted DDS may be a potential strategy for preventing and treating AD. Future studies in animal models of AD will be valuable to validate the therapeutic efficacy of the optimized nanosystem.
阿尔茨海默病（AD）是一种无法治愈的神经疾病，也是痴呆症的主要病因，其特征为β-淀粉样蛋白（Aβ）纤维沉积。咖啡酸（CA）因其抗淀粉样蛋白生成、抗炎和抗氧化特性，已显示出对AD治疗的潜在价值。然而，其化学不稳定性和有限的生物利用度限制了其在体内的治疗潜力。在此，通过不同技术制备了负载CA的脂质体。利用脑内皮细胞中转铁蛋白（Tf）受体的过表达，将Tf偶联到脂质体表面，以引导负载CA的纳米颗粒（NPs）到达血脑屏障（BBB）。优化后的Tf修饰的NPs平均粒径约为140 nm，多分散指数低于0.2，表面电荷呈中性，适合药物递送。Tf功能化脂质体显示出合适的包封效率和至少2个月的物理稳定性。此外，在模拟生理环境中，NPs可确保CA持续释放8天。研究了优化后的药物递送系统（DDS）的抗淀粉样蛋白生成功效。数据表明，负载CA的Tf功能化脂质体能够预防Aβ聚集和纤维形成，并使成熟纤维解聚。因此，所提出的脑靶向DDS可能是预防和治疗AD的潜在策略。未来在AD动物模型中的研究对于验证优化后的纳米系统的治疗效果将具有重要价值。
