阿尔茨海默病仍然是一个尚未解决的神经难题,无法治愈。目前的疗法只能缓解症状,通过血脑屏障的有限摄取阻碍。Auranofin,FDA批准的化合物,具有针对脑部疾病的有效抗氧化和抗炎特性。然而,其口服生物利用度的挑战促使探索基于纳米制剂的解决方案,提高血脑屏障的穿透性。本研究旨在探讨金诺芬纳米颗粒对链脲佐菌素诱导的AD大鼠的神经保护作用。通过多重乳液溶剂蒸发法配制了含金诺芬的聚乳酸-共-乙醇酸纳米颗粒。通过确定包封效率来进行表征,粒度分布,表面电荷,和形态学。通过施用链脲佐菌素(3mg/kg/i.c.v.,第1天和第3天),金诺芬(5和10毫克/千克),金诺芬纳米颗粒(2.5和5毫克/千克),和多奈哌齐(2mg/kg)口服14天。行为缺陷使用野外试验进行评估,莫里斯水迷宫,客观识别测试,氧化应激水平的变化,和大脑中的AD标记。老鼠被斩首后,切除大脑以分离海马体。随后的分析包括生化和神经炎症标志物的定量,以及神经递质水平的评估。金诺芬纳米粒子的表征显示了98%的包封率,平均粒径为101.5±10.3nm,表面电荷为27.5±5.10mV,多分散指数为0.438±0.12。在体内,服用金诺芬和金诺芬纳米颗粒可显着逆转链脲佐菌素诱导的认知缺陷,生化改变,神经炎症标记物,和神经递质水平。目前的发现表明,金诺芬纳米颗粒比单独的金诺芬具有更显著的神经保护潜力。治疗功效可能归因于其抗氧化和抗炎特性,以及其积极的神经调节作用。因此,我们的研究结果表明,它可能是阿尔茨海默病治疗的一个有希望的候选人。
Alzheimer\'s disease remains an unsolved neurological puzzle with no cure. Current therapies offer only symptomatic relief, hindered by limited uptake through the blood-brain barrier.
Auranofin, an FDA-approved compound, exhibits potent antioxidative and anti-inflammatory properties targeting brain disorders. Yet, its oral bioavailability challenge prompts the exploration of nanoformulation-based solutions enhancing blood-brain barrier penetrability. The study aimed to investigate the neuroprotective potential of auranofin nanoparticles in streptozotocin-induced AD rats.
Auranofin-containing polylactic-co-glycolic acid nanoparticles were formulated by the multiple emulsion solvent evaporation method. Characterization was done by determining entrapment efficiency, particle size distribution, surface charge, and morphology. An in vivo study was performed by administering streptozotocin (3 mg/kg/i.c.v., days 1 and 3),
auranofin (5 and 10 mg/kg), auranofin nanoparticles (2.5 and 5 mg/kg), and donepezil (2 mg/kg) for 14 days orally. Behavioral deficits were evaluated using the open field test, Morris water maze, objective recognition test, change in oxidative stress levels, and AD markers in the brain. Following the decapitation of the rats, the brains were excised to isolate the hippocampus. Subsequent analyses included the quantification of biochemical and neuroinflammatory markers, as well as the assessment of neurotransmitter levels. The characterization of auranofin nanoparticles showed an entrapment efficiency of 98%, an average particle size of 101.5 ± 10.3 nm, a surface charge of 27.5 ± 5.10 mV, and a polydispersity index of 0.438 ± 0.12. In vivo, administration of
auranofin and
auranofin nanoparticles significantly reversed streptozotocin-induced cognitive deficits, biochemical alteration, neuroinflammatory markers, and neurotransmitter levels. The present finding suggests that auranofin nanoparticles have more significant neuroprotective potential than
auranofin alone. The therapeutic efficacy may be attributed to its antioxidant and anti-inflammatory properties, as well as its positive neuromodulatory effects. Therefore, our findings suggest that it could be a promising candidate for Alzheimer\'s disease therapy.