Department of Pharmacology & Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, 21500, Egypt.
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21500, Egypt.
Nanomedicine (Lond). 2021 Jun;16(15):1281-1296. doi: 10.2217/nnm-2021-0051. Epub 2021 May 20.
Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.
加兰他敏是一种常用于阿尔茨海默病治疗的乙酰胆碱酯酶抑制剂。其胆碱能不良反应和快速消除限制了其治疗效果。我们研究了 2 周鼻腔给予结合壳聚糖纳米粒的加兰他敏（G-NP）治疗东莨菪碱诱导的阿尔茨海默病大鼠模型的药效学和药代动力学。评估了行为、神经生化和组织病理学变化，并与口服和鼻腔溶液进行了比较。使用新的经过验证的 LC/MS 测定法确定了脑摄取和药代动力学。G-NP 增强了大鼠的空间记忆、探索行为和胆碱能传递。抑制了β-淀粉样蛋白沉积和 Notch 信号转导，并恢复了组织病理学退化。G-NP 增强了加兰他敏的脑内递送并延迟了其消除。G-NP 具有有前途的治疗潜力和脑靶向性，优于传统的加兰他敏治疗。
