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Anti-inflammatory potential of simvastatin loaded nanoliposomes in 2D and 3D foam cell models
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2021-06-30 , DOI: 10.1016/j.nano.2021.102434
Moumita Rakshit 1 , Anastasia Darwitan 1 , Aristo Muktabar 1 , Prativa Das 1 , Luong T H Nguyen 2 , Ye Cao 1 , Catarina Vizetto-Duarte 1 , Jinkai Tang 1 , Yee Shan Wong 1 , Subbu Venkatraman 1 , Kee Woei Ng 3
Affiliation  

Atherosclerosis is a multifactorial disease triggered and sustained by risk factors such as high cholesterol, high blood pressure and unhealthy lifestyle. Inflammation plays a pivotal role in atherosclerosis pathogenesis. In this study, we developed a simvastatin (STAT) loaded nanoliposomal formulation (LIPOSTAT) which can deliver the drug into atherosclerotic plaque, when administered intravenously. This formulation is easily prepared, stable, and biocompatible with minimal burst release for effective drug delivery. 2D and 3D in vitro models were examined towards anti-inflammatory effects of STAT, both free and in combination with liposomes. LIPOSTAT induced greater cholesterol efflux in the 2D foam cells and significantly reduced inflammation in both 2D and 3D models. LIPOSTAT alleviated inflammation by reducing the secretion of early and late phase pro-inflammatory cytokines, monocyte adherence marker, and lipid accumulation cytokines. Additionally, the 3D foam cell spheroid model is a convenient and practical approach in testing various anti-atherosclerotic drugs without the need for human tissue.



中文翻译:

辛伐他汀负载纳米脂质体在 2D 和 3D 泡沫细胞模型中的抗炎潜力

动脉粥样硬化是一种多因素疾病,由高胆固醇、高血压和不健康的生活方式等风险因素触发和维持。炎症在动脉粥样硬化的发病机制中起关键作用。在这项研究中,我们开发了一种负载辛伐他汀 (STAT) 的纳米脂质体制剂 (LIPOSTAT),当静脉内给药时,它可以将药物输送到动脉粥样硬化斑块中。该配方易于制备、稳定且具有生物相容性,并且具有最小的突发释放,可有效地进行药物输送。2D 和 3D体外模型针对 STAT 的抗炎作用进行了检查,包括游离的和与脂质体组合的。LIPOSTAT 在 2D 泡沫细胞中诱导更大的胆固醇流出,并显着减少 2D 和 3D 模型中的炎症。LIPOSTAT 通过减少早期和晚期促炎细胞因子、单核细胞粘附标志物和脂质积累细胞因子的分泌来减轻炎症。此外,3D 泡沫细胞球体模型是一种方便实用的方法,无需人体组织即可测试各种抗动脉粥样硬化药物。

更新日期:2021-07-22
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