Simvastatin-loaded nano-niosomes confer cardioprotection against myocardial ischemia/reperfusion injury

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Abstract
Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system. Hence, this study aims to investigate therapeutic efficacy of SIM-loaded nano-niosomes on MI/R injury. Surface active agent film hydration method was used to synthesize nano-niosomes. The physicochemical properties of nano-niosomes were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, niosomes were characterized in entrapment efficiency (EE) and releasing pattern. Male Wistar rats were assigned into five groups (sham, MI/R, SIM, nano-niosomes, and SIM-loaded nano-niosomes). To induce MI/R, left thoracotomy was performed along mid-axillary line. The LAD ligation lasted for 45 min. A single dose (3 mg/kg) of drug formulations was injected into myocardial. Echocardiography was performed to evaluate cardiac function. The expression of the necroptosis markers was evaluated using western blot assay. Particle size of only nano-niosomes was about 137 nm, whereas a shift to 163 nm was observed in nano-niosomes containing SIM. Optimized niosomes were achieved by span 80, drug to cholesterol ratio of 0.4 with 7-min sonication time. EE of optimized nano-niosomes containing SIM was 98.21%. The effects of nano-niosomes containing on improving cardiac function and inhibiting necroptosis pathway was more efficient than the SIM group. Our findings have suggested that nano-niosomes can be applied as a notable drug delivery method to augment stability, bioavailability, and therapeutic efficacy of SIM, when it used against myocardial I/R injury. Graphical abstract

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