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Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats
Shin Yajima1, Shigeru Miyagawa1, Satsuki Fukushima1
1Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
JACC. Basic to Translational Science
|July 18, 2019
Summary
Intravenously injected ONO-1301 nanoparticles selectively target heart injury, reducing infarct size and improving blood flow. This drug delivery method enhances therapeutic effects for myocardial ischemia/reperfusion injury.
Area of Science:
- Cardiovascular Research
- Nanomedicine
- Pharmacology
Background:
- Myocardial ischemia/reperfusion (I/R) injury remains a significant clinical challenge.
- Effective drug delivery to the injured myocardium is crucial for therapeutic intervention.
Purpose of the Study:
- To evaluate the efficacy of ONO-1301-containing nanoparticles (ONO-1301NPs) in treating myocardial I/R injury in a rat model.
- To investigate the targeted accumulation and retention of ONO-1301NPs in the injured heart tissue.
Main Methods:
- Intravenous administration of ONO-1301NPs, ONO-1301 solution, or vehicle in rats subjected to myocardial I/R injury.
- Assessment of nanoparticle distribution, drug retention, infarct size, capillary network preservation, and myocardial blood flow.
- Analysis of proangiogenic and inflammatory cytokine expression in the ischemic myocardium.
Main Results:
- ONO-1301NPs selectively accumulated in the I/R-injured myocardium, with prolonged drug retention compared to ONO-1301 solution.
- Administration of ONO-1301NPs led to up-regulation of proangiogenic cytokines and down-regulation of inflammatory cytokines.
- ONO-1301NP-treated rats showed significantly smaller infarct size, better-preserved capillary networks, and improved myocardial blood flow at 24 hours post-I/R injury.
Conclusions:
- ONO-1301NPs effectively attenuate myocardial I/R injury.
- The therapeutic benefits are mediated through the proangiogenic and anti-inflammatory actions of ONO-1301 delivered via nanoparticles.
- Targeted nanoparticle delivery enhances drug efficacy for myocardial I/R injury treatment.
Keywords:
ANG, angiopoietinEPR, enhanced permeability and retentionI/R, ischemia/reperfusionIL, interleukinMBF, myocardial blood flowMRI, magnetic resonance imagingNP, nanoparticleONO-1301PET, positron emission tomographyPMNL, polymorphonuclear leukocyteVEGF, vascular endothelial growth factorischemia/reperfusion injurynanoparticlesprostacyclin
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