Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Life Sci. 2021 Jun 1;274:119344. doi: 10.1016/j.lfs.2021.119344. Epub 2021 Mar 11.
Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities.
Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied.
Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (-14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ < 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ < 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated.
Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.
胺碘酮（AM）是一种治疗心律失常的高效药物，但它的心脏外不良反应抵消了其治疗效果。基于纳米粒子（NPs）的给药系统可以提供一种策略，使 AM 能够持续递送到心肌并减少不良反应。主要目的是开发 AM 负载的 NPs，并探索其对非靶毒性的改善作用。
使用聚丙交酯-共-乙交酯制备聚合物 NPs，并对其理化性质进行了表征。使用大鼠模型进行动物研究，比较 AM 与 AM 负载的 NPs 的暴露情况。通过测定肝酶、血脂谱和甲状腺激素来评估生物化学。此外，还研究了肝和肺的组织病理学变化。
在最佳实验条件下，AM 负载的 NPs 的大小为 186.90nm，且具有负的 zeta 电位（-14.67mV）。AM 处理动物组的生化评估显示胆固醇、TG、LDL、T4 和 TSH 水平显著升高（ρ<0.05）。值得注意的是，AM 处理组的肝酶显著升高（ρ<0.05），同时肝结构发生明显变化。AM 负载的 NPs 显示出减轻肝损伤和酶水平的作用。AM 处理组的肺组织显示出肺泡间隔增厚、单核细胞浸润伴充血血管以及大量胶原纤维沉积。相反，在 AM 负载的 NPs 处理的动物肺中观察到较少的细胞浸润和间隔增厚。
我们的研究结果表明，AM 负载的 NPs 能够为规避 AM 诱导的非靶毒性开辟新的途径。
