Fabrication and evaluation of spironolactone-loaded nanostructured lipid carries for cardiac tissue regeneration

Abstract

Background: 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. Method: 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). Results: 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. Conclusion: 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.

Keywords

• cardiac tissue regeneration
• nanostructures lipid carriers
• spironolactone
• sustain release