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

Abstract

PurposeMyocardial 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 methodsOleate 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.ResultsIn 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.ConclusionThese results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.

Salviae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection Protects Against Myocardial Ischemia-Reperfusion Injury and Heart Failure

“…ANP/PKG signaling pathway can regulate the K ATP channel of ventricular cardiomyocytes [40]. ANP modi ed adenosine oleate precursor drugs have a better therapeutic effect on acute myocardial ischemia in rats [41]. In this study, SGI signi cantly inhibited the expressions of ANP and BNP mRNA, and signi cantly reduced the expressions of SP1 and GATA4 mRNA at the upstream and Prkg1a mRNA at the downstream, suggesting that SGI can play a protective role on the heart by inhibiting ANP and BNP.…”

Acute myocardial infarction therapy: in vitro and in vivo evaluation of atrial natriuretic peptide and triphenylphosphonium dual ligands modified, baicalin-loaded nanoparticulate system

“…Yu et al. ( 2018 ) suggested that nanoparticles could elongate the circulation time of drugs in serum and have great potential to accumulate in the myocardial infarct area. The higher heart distribution of ANP/TPP-BN-LPNs than non-modified LPNs is in accordance with the aim of the study: to deliver more nanocarriers to the heart.…”

“…ANP contained ligand was synthesized by conjugating APN-NH 2 to DSPE-PEG by amide bond to achieve ANP-PEG-DSPE (Yu et al., 2018 ). Briefly, EDC·HCl (1.2 equivalents) and NHS (1.2 equivalents) were added to DSPE-PEG (1 equivalent), stirred for 2 h to activate the carboxyl groups (solution A).…”

Recent Advances in Nanomaterials for Therapy and Diagnosis of Cardiovascular Disease

“…NPs have longer circulated properties than free drugs and can be targeted into the infarcted myocardium in a receptordependent process [80].…”

“…Further study is needed to comprehensively analyze the toxicity, especially chemotoxicity and inflammatory responses. In addition, future work should plan to introduce novel ways to reduce toxicity, represented in Table 3 [77][78][79][80][81][82][83][84][85] and Table 4 [86][87][88][89].…”