Cycloastragalol nanoparticle-loaded composite hydrogel as an injectable embolic agent for vascular repair in a mouse model of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a progressive degenerative vascular disease with a high risk of rupture and mortality. Endovascular aneurysm repair (EVAR) is a widely used minimally invasive treatment option for anatomically suitable AAA. However, postoperative endoleaks associated with EVAR can precipitate secondary aneurysm rupture. We developed an injectable nanocomposite hydrogel for embolization and local delivery of cycloastragalol (CAG). CAG-loaded aldehyde-functionalized polyurethane nanoparticles (DFPU@CAG) showed uniform morphology, favorable biocompatibility, and enhanced CAG delivery efficiency, and were incorporated into a chitosan (CS)-based dynamically crosslinked hydrogel to form CS-DFPU@CAG. The hydrogel showed suitable injectability and rheological properties for embolization with sustained local drug release. In vivo studies in animal AAA models showed that in situ administration significantly attenuated AAA expansion and reduced matrix metalloproteinase9 (MMP9) expression and enzymatic activity. CS-DFPU@CAG also demonstrated robust embolization performance in vitro and in vivo, maintaining stability under high pressure and achieving blood-flow occlusion in rabbit femoral arteries comparable to a clinical porcine fibrin sealant. These findings provide a preclinical proof-of-concept for CS-DFPU@CAG as a dual-function embolic and local therapeutic platform for AAA management.

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