Falak Mehrzad, Mehdikhani Mehdi, Varshosaz Jaleh, Hashemibeni Batool, Ebrahimian-Hosseinabadi Mehdi
Department of Biomedical Engineering, Faculty of Engineering, University of Isfahan, Isfahan, Iran.
Department of Pharmaceutics, Novel Drug Delivery Systems Research Centre, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
J Med Signals Sens. 2020 Nov 11;10(4):260-265. doi: 10.4103/jmss.JMSS_46_19. eCollection 2020 Oct-Dec.
Spironolactone (SP) is a lipophilic aldosterone receptor antagonist that few studies have reported its effect on cardiac remodeling. In addition, fewer researches have considered its influence on cardiomyocyte viability and potential benefits for myocardial tissue remodeling.
In this study, stearic acid (SA) (solid lipid) and oleic acid (OA) (liquid lipid) were utilized to produce nanostructured lipid carries (NLCs) (various ratios of SA to OA and water amount, F1: 80:20 [30 ml water], F2: 80:20 [60 ml water], F3: 70:30 [30 ml water], and F4: 70:30 [60 ml water]) containing SP and their particle size, polydispersity index, zeta potential, entrapment efficiency, and release profile were measured. The purpose of encapsulating SP in NLCs was to provide a sustain release system. Meanwhile, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with different concentrations of SP-loaded NLCs (SP-NLCs) was conducted to evaluate the cytotoxicity of the NLCs on rat myocardium cells (H9C2).
Increase of oil content to 10 wt% reduced the particle size from 486 nm (F1) to 205 nm (F2). Zeta potential of the samples at around -10 mV indicated their agglomeration tendency. After 48 h, SP-NLCs with the concentrations of 5 and 25 μM showed significant improvement in cell viability while the same amount of free SP-induced cytotoxic effect on the cells. SP-NLCs with higher concentration (50 μM) depicted cytotoxic effect on H9C2 cells.
It can be concluded that 25 μM SP-NLCs with sustain release profile had a beneficial effect on cardiomyocytes and can be used as a mean to improve cardiac tissue regeneration.
螺内酯（SP）是一种亲脂性醛固酮受体拮抗剂，鲜有研究报道其对心脏重塑的影响。此外，考虑其对心肌细胞活力及心肌组织重塑潜在益处的研究更少。
在本研究中，使用硬脂酸（SA）（固体脂质）和油酸（OA）（液体脂质）制备载有SP的纳米结构脂质载体（NLCs）（SA与OA的不同比例及水量，F1：80:20 [30毫升水]，F2：80:20 [60毫升水]，F3：70:30 [30毫升水]，以及F4：70:30 [60毫升水]），并测量其粒径、多分散指数、ζ电位、包封率及释放曲线。将SP包封于NLCs中的目的是提供一个缓释系统。同时，采用不同浓度的载SP纳米结构脂质载体（SP-NLCs）进行噻唑蓝比色法试验，以评估NLCs对大鼠心肌细胞（H9C2）的细胞毒性。
油含量增加至10 wt%使粒径从486纳米（F1）减小至205纳米（F2）。样品的ζ电位在-10 mV左右表明其有团聚倾向。48小时后，浓度为5和25 μM的SP-NLCs显示细胞活力有显著改善，而相同剂量的游离SP对细胞有细胞毒性作用。较高浓度（50 μM）的SP-NLCs对H9C2细胞表现出细胞毒性作用。
可以得出结论，具有缓释特性的25 μM SP-NLCs对心肌细胞有有益作用，可作为改善心脏组织再生的一种手段。
