Evaluation of cardioprotective effect of naringin loaded lignin nanoparticles against isoproterenol induced myocardial infarction

Myocardial infarction (MI) is a severe manifestation of ischemic heart disease (IHD) that impacts cardiac functions. Naringin is a bioflavonoid also known as 4-trihydroxy-flavonone-7-rhamnoglucoside, that offers numerous pharmacological benefits including antidiabetic, cardioprotective, and neuroprotective activities. Despite its benefits, the poor water solubility of naringin limits its drug delivery application. The objective of the investigation is to develop, optimize and evaluate the nanoparticles loaded with naringin (NR-LGNPs) by using lignin and Tween 80 as polymers and stabilizers, respectively. The NR-LGNPs were prepared using a modified phase separation technique while the composition as well as process variables of the NR-LGNPs were optimized using 23 factorial design of the experiment. The optimized formulation was subsequently characterized for various in vitro and in vivo parameters. The formulated optimized polymeric nanoparticles were spherical and had a size of 138.24 +/- 1.36 nm with entrapment efficiency of 91.53 +/- 0.84 %. The in vitro drug release was found to be 88.75 +/- 1.54 % at the end of 24 h. The administration of LG-NPs at a dosage of 10 mg/kg through intravenous injection demonstrated a significant ability to mitigate the levels of creatine kinase-myoglobin binding (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), lipid peroxidation (MDA) following in vivo animal model. The tissue histopathology study indicated the significant potential for restoration of cardiac tissue damage upon treatment with NR-LGNPs. Additionally, it was observed that the treatment with LG-NPs improved the size of the cardiac infarction, indicating its potent cardioprotective activity to combat myocardial damage induced by ISO. Thus, the enhancement of NR bioactivity through nanotechnology could potentially mitigate cardiac damage due to myocarial infarction.