## 1 Introduction  
Renal ischemia/reperfusion (I/R) accrues from a decrease in total or regional renal blood flow, followed by consequent restoration [1]. Various clinical conditions such as cardiac surgery, sepsis, trauma and kidney transplantation may lead to renal ischemia [2]. Ischemia-derived hypoxia results in tissue damages, reactive oxygen species (ROS) production, tubular epithelium necrosis, reduced glomerular filtration and inflammatory responses [3, 4]. Although reperfusion is essential for the survival of ischemic kidney tissue, it was shown that restoring blood flow can exacerbate tissue damage [1]. There are various strategies to prevent I/R injury; meanwhile, this complication can lead to high mortality [5]. Consequently, newly developed therapeutic drugs and interventions addressed to the prevention of I/R-induced renal injuries are strongly pursued. Evidence suggests that imbalance between vasoconstretrics and vasodilators may lead to decreased reperfusion [6]. Therefore, the design of drugs that regulate factors affecting tissue blood flow can play an important role in preventing damage caused by renal ischemia. The aldosterone hormone regulates the concentration of sodium and potassium ions in the blood by affecting target organs, including the intestines and kidneys. It also has a vasoconstretric effect on the renal vasculature system. Since the effects of this hormone are mediated through mineralocorticoid receptors, blocking mineralocorticoid receptors may play a supportive role in reducing the destructive effects of circulatory disorders on kidney tissue and other ischemic organs. Specifically, recent studies have shown that the aldosterone exacerbates the destructive effects of renal I/R [7; 8]. Based on these findings, clinical observations showed that the use of mineralocorticoid blockers improves the damage caused by renal ischemia. The protective effects of mineralocorticoid antagonists have been documented in several models of nephropathy, including diabetic rats [9], ureteral obstruction [10] and aldosteronene-treated rats [11]. In addition, in cases of cyclosporine A-induced nephrotoxicity, administration of mineralocorticoid blockers reduces the destructive effects of cyclosporine use. Indeed, the destructive effects of cyclosporine A are due to the reduction of renal blood flow because aldosteronene acts as a vasoconstretric; therefore, the destructive effects of cyclosporine are augmented by aldosteronene [12]. Several studies have demonstrated that spironolactone (SP) as a mineralocorticoid antagonist plays an important role in preventing the physiopathology of renal injuries [13; 14]. For example, there are several reports showing the beneficial effects of SP in animal models of kidney damage induced by diabetes [15], ischemia [13] and obstructive jaundice [16]. Furthermore, low doses of SP carry advantages to patients with chronic kidney disease [17]. Clinically, the benefit of SP is achieved only with long-term use via oral route, which is often associated with side effects of gynecomasia, menstrual irregularities and decreased libido. Moreover, spironolactone is characterized by incomplete oral behavior because of its low solubility and slow dissolution rate [18]. Liposome drug delivery systems have shown encouraging results in altering the bioavailability of encapsulated therapeutic agents, thus improving the drug therapeutic index in terms of longevity, drug safety profiles, therapeutic efficacy and distribution characteristics [19; 20; 21]. It has been shown that liposome-encapsulated SP has therapeutic/preventive potential for acute lung injury and fibrosis in mice [22]. Furthermore, optimizing SP by nanoprecipitation method leads to minimizing the preparation volume administered for children medication [18]. Another report shows promising results of SP-loaded leciplexes in the treatment of female acne [23].