Zewail Moataz B, Nomier Yousra A, E Elesawy Ahmed, El-Dakroury Walaa A
School of Chemical Engineering, Faculty of Sciences, Engineering and Technology, The University of Adelaide, Adelaide, SA 5005, Australia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Int J Biol Macromol. 2025 Aug;319(Pt 3):145569. doi: 10.1016/j.ijbiomac.2025.145569. Epub 2025 Jun 26.
Phytochemicals have emerged as promising candidates for next-generation therapeutics targeting neurological disorders. Among them, quercetin (QU) has shown potential in alleviating depression and preventing cognitive decline. However, its clinical utility is limited by poor oral bioavailability and restricted permeability across the blood-brain barrier (BBB). To address these challenges, QU was encapsulated in chitosan-coated nanostructured lipid carriers (QU-CS-NLCs), forming a novel nano-system to enhance brain-directed delivery and therapeutic efficacy. QU-CS-NLCs exhibited nanometric particle size, sustained-release behavior, and structural integrity, as confirmed by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Superior therapeutic efficacy of QU-CS-NLCs over pure QU and the standard antidepressant fluoxetine was observed in a lipopolysaccharide (LPS) -induced mouse model of depression and anxiety. Behavioral assays revealed improved mood and anxiety parameters, including increased sucrose preference, prolonged struggle time, and reduced immobility. Moreover, QU-CS-NLCs led to a 65.4 % reduction in C-reactive protein (CRP), a 145.2 % increase in brain serotonin, and a 331.8 % increase in brain-derived neurotrophic factor (BDNF), alongside restoration of TrkB receptor expression. Histopathological analysis further confirmed significant neuroprotective effects. These findings underscore the enhanced antidepressant potential of QU-CS-NLCs, offering a promising alternative to conventional QU or Fluoxetine therapies.
植物化学物质已成为治疗神经疾病的下一代有前景的候选药物。其中，槲皮素（QU）在缓解抑郁和预防认知衰退方面已显示出潜力。然而，其临床应用受到口服生物利用度差和血脑屏障（BBB）通透性受限的限制。为应对这些挑战，将QU包裹在壳聚糖包被的纳米结构脂质载体（QU-CS-NLCs）中，形成一种新型纳米系统，以增强脑靶向递送和治疗效果。傅里叶变换红外（FT-IR）光谱、差示扫描量热法（DSC）和X射线衍射（XRD）证实，QU-CS-NLCs具有纳米级粒径、缓释行为和结构完整性。在脂多糖（LPS）诱导的抑郁和焦虑小鼠模型中，观察到QU-CS-NLCs比纯QU和标准抗抑郁药氟西汀具有更好的治疗效果。行为学分析显示情绪和焦虑参数得到改善，包括蔗糖偏好增加、挣扎时间延长和不动时间减少。此外，QU-CS-NLCs使C反应蛋白（CRP）降低65.4%，脑血清素增加145.2%，脑源性神经营养因子（BDNF）增加331.8%，同时恢复了TrkB受体表达。组织病理学分析进一步证实了显著的神经保护作用。这些发现强调了QU-CS-NLCs增强的抗抑郁潜力，为传统的QU或氟西汀疗法提供了一种有前景的替代方案。
