Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

PURPOSE: Myocardial infarction is a major cause of mortality and heart failure worldwide. One of the most effective methods of this injury is direct delivery of cardioprotective drugs to ischemia–reperfusion (IR) myocardium. The aim of the present study was to fabricate an adenosine (Ade) prodrug-based, atrial natriuretic peptide (ANP)-modified nanosystem for the treatment of myocardial infarction. MATERIALS AND METHODS: Oleate adenosine prodrug (Ade-OA) and ANP-distearoylphosphatidylethanolamine-polyethylene glycol were synthesized. ANP-modified Ade-loaded lipid nanocarriers (ANP Ade/LNCs) were then self-assembled by using solvent evaporation method. In vitro drug release in the presence of plasma was evaluated. In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics were investigated in rats with ischemic myocardium after intravenous injection. RESULTS: In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics studies in acute myocardial infarction (AMI) rats showed that ANP Ade/LNCs exhibited better efficiency than non-modified Ade/LNCs and free Ade in all respects. CONCLUSION: These results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.