Xu Guangzhe, Ma Chun, Chu Hongyan, Hu Wenxin, Yang Lihua, Li Shuling
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, People's Republic of China.
Department of Geriatrics, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People's Republic of China.
Int J Nanomedicine. 2025 Mar 25;20:3825-3842. doi: 10.2147/IJN.S508800. eCollection 2025.
The pathological mechanisms underlying ischemic stroke are highly complex, with the neuroinflammatory response triggered by cerebral ischemia-reperfusion being a major contributor to secondary brain damage. This response significantly impedes neural tissue regeneration. Despite advancements in treatment, current anti-inflammatory strategies remain suboptimal in terms of safety and efficacy. This study aimed to develop an all-natural nanomedicine delivery system for the transnasal administration of puerarin, combined with the endogenous anti-inflammatory peptide Ac2-26, to enhance neuroprotection against ischemic stroke through a synergistic anti-inflammatory approach.
In this study, collagen nanoparticles (PueNps) loaded with puerarin were synthesized, followed by the preparation of a chitosan hydrogel. The PueNps and Ac2-26 were co-encapsulated within the hydrogel, resulting in the formation of the PueNps&Ac2-26 gel formulation. The physicochemical properties of this formulation, as well as its biodistribution and anti-ischemic efficacy in the MCAO rat brain, were evaluated.
In this formulation system, the bioavailability of puerarin and Ac2-26 was enhanced, exhibiting sustained-release properties, which enabled efficient brain-targeted delivery. It effectively alleviated neurological impairment in MCAO rats, reduced the volume of cerebral infarction, and decreased brain water content. Additionally, the PueNps&Ac2-26 gel significantly inhibited neuroinflammation in rats and alleviated oxidative stress.
The PueNps&Ac2-26 gel is a purely natural and efficient formulation system, offering a promising approach for the clinical treatment of ischemic stroke in the future.
缺血性中风的病理机制高度复杂，脑缺血再灌注引发的神经炎症反应是继发性脑损伤的主要促成因素。这种反应显著阻碍神经组织再生。尽管治疗取得了进展，但目前的抗炎策略在安全性和有效性方面仍不尽人意。本研究旨在开发一种全天然纳米药物递送系统，用于经鼻给药葛根素，并结合内源性抗炎肽Ac2-26，通过协同抗炎方法增强对缺血性中风的神经保护作用。
在本研究中，合成了负载葛根素的胶原纳米粒（PueNps），随后制备壳聚糖水凝胶。将PueNps和Ac2-26共包封在水凝胶中，形成PueNps&Ac2-26凝胶制剂。评估了该制剂的理化性质及其在大脑中动脉闭塞（MCAO）大鼠脑中的生物分布和抗缺血疗效。
在该制剂系统中，葛根素和Ac2-26的生物利用度提高，具有缓释特性，能够实现有效的脑靶向递送。它有效减轻了MCAO大鼠的神经功能缺损，减小了脑梗死体积，降低了脑含水量。此外，PueNps&Ac2-26凝胶显著抑制大鼠神经炎症并减轻氧化应激。
PueNps&Ac2-26凝胶是一种纯天然且高效的制剂系统，为未来缺血性中风的临床治疗提供了一种有前景的方法。
