Abstract
The incidence of heart failure (HF) is increasing worldwide and myocardial infarction (MI), which follows ischemia and reperfusion (I/R), is often at the basis of HF development. Nanocarriers are interesting particles for their potential application in cardiovascular disease. Impaired drug delivery in ischemic disease is challenging. Cyclodextrin nanosponges (NS) can be considered innovative tools for improving oxygen delivery in a controlled manner. This study has developed new α-cyclodextrin-based formulations as oxygen nanocarriers such as native α-cyclodextrin (α-CD), branched α-cyclodextrin polymer (α-CD POLY), and α-cyclodextrin nanosponges (α-CD NS). The three different α-CD-based formulations were tested at 0.2, 2, and 20 µg/mL to ascertain their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) in vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to normoxia (20% oxygen) or hypoxia (5% CO2 and 95% N2). The different formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15% to 30%) when compared to samples devoid of oxygen. Moreover, their application at the beginning of reoxygenation induced a considerable reduction in cell death (12% to 20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment.
Highlights
Advanced and smart polymer-based nanocarriers were designed for tissue-specific targeted delivery, triggered release, and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics
Hypoxia is a pathological condition for many diseases and it occurs in acute coronary occlusion, which leads to cardiac cell death
Since nanoparticle approaches for oxygen delivery are theoretically feasible, this study aimed at testing the protective potential of cyclodextrin-based nanoparticles that can deliver oxygen in a highly controlled manner
Summary
Advanced and smart polymer-based nanocarriers were designed for tissue-specific targeted delivery, triggered release, and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. The heart is a metabolically demanding organ and mismatches between supply and demand of oxygen may occur, which could lead to hypoxia and cardiac cell distress. Hypoxia is a pathological condition for many diseases and it occurs in acute coronary occlusion, which leads to cardiac cell death. This is the first phase of acute myocardial infarction (AMI). Hypertrophic surviving cells and heart failure are consequences of AMI. These serious outcomes of coronary occlusion can be limited by early and beneficial reperfusion.
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