Nematalla Hisham A, Elharoun Mona, Bargash Somaia N, Abd-Alhaseeb Mohammad M, Sharafeldin Hend A, Zewail Mariam, Abbas Haidy, Elsheikh Manal A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Int J Pharm. 2025 Feb 10;670:125197. doi: 10.1016/j.ijpharm.2025.125197. Epub 2025 Jan 8.
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by motor and non-motor symptoms, with limited effective treatment options. This study proposes a novel approach utilizing intranasal delivery of carbenoxolone (CBX) via chitosan-coated solid lipid nanoparticles (CS-coated SLNs) to manage PD symptoms by enhancing CBX delivery and brain targeting. Formulated CS-coated SLNs exhibited favorable quality attributes including particle size (164 ± 0.12 nm), surface charge (18 ± 0.89 mV), high entrapment efficiency (97.98 ± 0.98 %), and sustained drug release profile. In vivo evaluations in a rotenone-induced rat model of PD involved intranasal administration of CBX suspension and CBX-loaded CS-coated SLN (equivalent to 20 mg/kg/day) over four weeks. The CBX nano-formulation group showed significant improvements in motor function, coordination, and balance, as well as modulation of neurotransmitter levels, with increased dopamine and decreased α-synuclein levels compared to the control group. Moreover, the CBX nano-formulation exhibited superior efficacy in reducing neuroinflammation, oxidative stress, and apoptosis markers. Histological examination revealed restored neuronal architecture, suggesting potential neuroprotective effects. In conclusion, mucoadhesive chitosan-coated SLNs offer a promising nasal delivery system overcoming brain drug delivery obstacles facing CBX therapy in PD, paving the way to the development of novel treatments and improved quality of life for PD patients.
帕金森病（PD）是一种使人衰弱的神经退行性疾病，其特征为运动和非运动症状，有效治疗选择有限。本研究提出了一种新方法，即通过壳聚糖包被的固体脂质纳米粒（CS包被的SLNs）经鼻递送羧苄青霉素（CBX），以通过增强CBX递送和脑靶向作用来控制PD症状。所制备的CS包被的SLNs表现出良好的质量属性，包括粒径（164±0.12 nm）、表面电荷（18±0.89 mV）、高包封率（97.98±0.98%）和持续的药物释放曲线。在鱼藤酮诱导的PD大鼠模型中的体内评估包括在四周内经鼻给予CBX悬浮液和载有CBX的CS包被的SLN（相当于20 mg/kg/天）。与对照组相比，CBX纳米制剂组在运动功能、协调性和平衡方面有显著改善，神经递质水平也得到调节，多巴胺水平升高，α-突触核蛋白水平降低。此外，CBX纳米制剂在降低神经炎症、氧化应激和细胞凋亡标志物方面表现出优异的疗效。组织学检查显示神经元结构恢复，表明具有潜在的神经保护作用。总之，粘膜粘附性壳聚糖包被的SLNs提供了一种有前景的经鼻给药系统，克服了CBX治疗PD时面临的脑药物递送障碍，为开发新的治疗方法和改善PD患者的生活质量铺平了道路。
