Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, and Institute of Biomaterials, University of Tehran and Tehran University of Medical Sciences (IBUTUMS), Tehran, Iran.
Sci Rep. 2023 Aug 24;13(1):13880. doi: 10.1038/s41598-023-41136-y.
In the study, a biomimetic platform for anti-inflammatory-based treatment of atherosclerotic plaque was developed. Gliclazide (GL) as an anti-inflammasome agent was encapsulated in PLGA nanoparticles (NP), which were coated by monocyte membrane using an extrusion procedure. The size and zeta potential of the nanoghost (NG) changed to 292 and - 10 nm from 189.5 to -34.1 in the core NP. In addition, the actual size of 62.5 nm with a coating layer of 5 nm was measured using TEM. The NG was also showed a sustained release profile with the drug loading content of about 4.7%. Beside to attenuated TNFα, decrease in gene expression levels of NLRP3, MyD88, NOS, IL-1β, IL-18 and caspases 1/3/8/9 in LPS-primed monocytes exposed to NG strongly indicated remarkable inflammation control. After systemic toxicity evaluation and pharmacokinetic analysis of NP and NG, intravenous NG treatment of rabbits with experimentally induced atherosclerosis revealed remarkably less plaque lesions, foam cells, lipid-laden macrophages, and pathological issues in tunica media of aorta sections. Higher expression of CD163 than CD68 in aorta of NG-treated rabbits strongly reveals higher M2/M1 macrophage polarization. The bio/hemocompatible, biomimetic and anti-inflammatory NG can be considered as a potential platform for immunotherapy of particularly atherosclerosis in the field of personalized medicine.
在这项研究中，开发了一种基于抗炎的抗动脉粥样硬化斑块治疗的仿生平台。格列齐特 (GL) 作为一种抗炎症小体药物被包裹在 PLGA 纳米颗粒 (NP) 中，然后通过挤出程序用单核细胞膜包裹 NP。纳米幽灵 (NG) 的粒径和zeta 电位从核心 NP 的 189.5nm 和 -34.1mV 分别变为 292nm 和 -10mV。此外，使用 TEM 测量得到的实际尺寸为 62.5nm，涂层厚度为 5nm。NG 还显示出药物负载量约为 4.7%的持续释放曲线。除了减弱 TNFα 外，暴露于 NG 的 LPS 预处理单核细胞中 NLRP3、MyD88、NOS、IL-1β、IL-18 和 caspase 1/3/8/9 的基因表达水平下降强烈表明炎症得到了显著控制。在对 NP 和 NG 进行系统毒性评估和药代动力学分析后，对实验性动脉粥样硬化兔进行静脉内 NG 治疗，发现斑块病变、泡沫细胞、载脂巨噬细胞和主动脉中层的病理问题明显减少。与 NG 治疗的兔主动脉中的 CD68 相比，CD163 的表达更高，强烈表明 M2/M1 巨噬细胞极化程度更高。生物/血液相容性、仿生和抗炎的 NG 可被视为个性化医学领域中动脉粥样硬化免疫治疗的潜在平台。
