Enalaprilat-loaded polyphenol nanoparticle composite hydrogel promotes myocardial protection after acute infarction

Heart failure (HF) has been increasing in morbidity and mortality worldwide, and one of the important causes of heart failure is myocardial infarction (MI), in which the coronary arteries are unable to provide sufficient blood flow to myocardial tissues, leading to necrosis and apoptosis, activation of inflammatory responses and neuroendocrine systems such as renin-angiotensin-aldosterone system (RAAS), generation of adverse ventricular remodeling, and finally the development of heart failure. In this paper, a drug-loaded polyphenol nanoparticles (ESaB NPs) containing active Angiotensin-converting enzyme inhibitor (ACEI) drugs enalaprilat and salvianolic acid B have been designed for the pathologic characteristics of acute MI. On this basis, a collagen/fucoidan hydrogel with good bioactivity and mechanical properties has been prepared, and the nanoparticles are incorporated into the aforementioned hydrogel to obtain a composite hydrogel (Gel-ESaB) with multiple synergistic therapeutic functions. The introduction of fucoidan can not only improve the mechanical strength and injectability of the collagen-based hydrogel, but also confer the collagen material with anticoagulant properties that are essential for future clinical applications as cardiovascular biomaterials. While providing mechanical support to the infarct site, the ESaB NPs delivered in situ to the infarct site play a key role in protecting myocardial tissue and restoring cardiac function through ROS scavenging, inflammation alleviation and tissue RAAS inhibitory ability. Both in vitro and in vivo experiments have confirmed the excellent therapeutic ability of Gel-ESaB in the treatment of MI and the prevention of HF after MI, which is expected to be an effective approach for MI treatment.