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基于壳寡糖/聚乳酸-羟基乙酸共聚物的白藜芦醇负载纳米颗粒预防博来霉素诱导的实验大鼠模型肺部炎症的新型简便高效途径

A Novel Facile and Efficient Prophylaxis Avenue of Chitosan Oligosaccharide/PLGA Based Polydatin Loaded Nanoparticles Against Bleomycin-Induced Lung Inflammation in Experimental Rat Model.

作者信息

Alnagar Ahmed Nashaat, Motawea Amira, Zaghloul Randa A, Eldesoqui Mamdouh, Abu Hashim Irhan Ibrahim

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Dakahlia, Egypt.

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Dakahlia, Egypt.

出版信息

AAPS PharmSciTech. 2025 Jan 16;26(1):35. doi: 10.1208/s12249-024-03022-2.

Abstract

Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects. Its clinical applications are hindered due to poor aqueous solubility, low bioavailability, and rapid metabolism by first-pass effect. Herein, we report the development of a novel chitosan oligosaccharide-coated PD-loaded Poly dl-lactide-co-glycolide nanoparticles (COS-coated PD/PLGA NPs) against a bleomycin-induced pulmonary inflammation in a rat model. The NPs exhibited a small particle size of 188.57 ± 5.68 nm and a high zeta potential of + 18.13 ± 2.75 mV with spherical architecture and sustained release pattern of PD. In vivo studies in bleomycin-induced lung inflammation in a rat model revealed the superior prophylactic activity of COS-coated PD/PLGA NPs over the free drug (PD) as demonstrated by histopathological and immunohistochemical analyses, alongside biochemical assays evaluating oxidative stress biomarkers and inflammatory cytokine levels. Overall, the optimized COS-coated PD/PLGA NPs formulation offers a promising prophylactic platform against many respiratory diseases.

摘要

肺部炎症是多种呼吸系统疾病的一个标志。尽管合成抗炎药具有很高的疗效,但它们会引起潜在的副作用。白藜芦醇苷(PD)是一种天然植物药,具有抗氧化和抗炎作用。由于其水溶性差、生物利用度低以及首过效应导致的快速代谢,其临床应用受到阻碍。在此,我们报告了一种新型壳寡糖包被的载PD聚(消旋)-丙交酯-共-乙交酯纳米颗粒(COS包被的PD/PLGA NPs)的研发,该纳米颗粒用于对抗博来霉素诱导的大鼠肺部炎症模型。这些纳米颗粒呈现出188.57±5.68nm的小粒径和+18.13±2.75mV的高zeta电位,具有球形结构和PD的缓释模式。在博来霉素诱导的大鼠肺部炎症模型中的体内研究表明,通过组织病理学和免疫组织化学分析以及评估氧化应激生物标志物和炎性细胞因子水平的生化测定,COS包被的PD/PLGA NPs比游离药物(PD)具有更好的预防活性。总体而言,优化后的COS包被的PD/PLGA NPs制剂为对抗多种呼吸系统疾病提供了一个有前景的预防平台。

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