DNAzyme loaded nano-niosomes attenuate myocardial ischemia/reperfusion injury by targeting apoptosis, inflammation in a NF-κB dependent mechanism.

ABSTRACT

Although DNAzymes have been found to reduce injury after myocardial ischemia/reperfusion (MI/R), their efficiency have been limited due to rapid degradation in vivo. Thus, this study was conducted to extend their half-life by encapsulation into nano­niosomes and examine their cardioprotective effects in a rat model of myocardial infarction (MI). In order to synthesize nano­niosomes, surface active agent film hydration method was used. Characterization of nano­niosomes was performed using the atomic force microscopy (AFM). In order to establish MI/R model in rats, left anterior descending coronary artery (LAD) was ligated for 30 min. A single dose (150µL) of drug formulations was injected into the infarcted region. The cardiac function was evaluated using echocardiography. The expression of pro-inflammatory cytokines, apoptotic factors, and nuclear factor-κB (NF-κB) were evaluated using Western blot and immunohistochemistry, respectively. Particle size of only nano-niosomes was in the range of 60-90 nm, while a shift to 70-110 nm was seen after DNAzyme encapsulation. MI rats treated with DNAzyme­loaded nano­niosomes could markedly reduce Bax, caspase3, TNF-α, IL-1ß, and NF-κB as well as increase Bcl-2 compared to only MI/R group. Collectively, our finding show that nano­niosomes can be considered excellent drug delivery platforms to extend half-life and stability of DNAzyme, when it is used to reduce myocardial I/R injury.