Plaque‐Specific Adhesive Balloons Coated with Calcium Phosphate Nanoparticles Loaded with Rapamycin for Atherosclerosis Therapy

Abstract Drug‐coated balloons (DCBs), serving as a superior alternative to stents, are at the cutting edge of clinical innovations in atherosclerosis management. Nevertheless, the prevalent high flow rates in arterial vascular result in short drug residence times, significantly compromising DCBs’ therapeutic effectiveness. Drawing inspiration from the mechanisms of vascular calcification, a rapamycin‐loaded calcium phosphate nanoparticle (CaP@Rapa) coating for balloons is pioneered. This coating functions as a potent drug anchor in arteries, facilitating the adhesion of rapamycin to plaques and thereby enhancing the local concentration of the rapamycin. To evaluate its therapeutic efficacy in vivo, the rabbit iliac artery atherosclerosis model is innovatively developed, which authentically mirrors the pathological progression of atherosclerosis in humans. The enhanced localized rapamycin retention, along with its pH‐sensitive sustained release characteristics, culminate in substantial reductions in plaque volume, a decrease in intimal hyperplasia, and mitigation of local inflammation in model rabbits. To further substantiate the translational potential of CaP@Rapa balloons, the research on the pig coronary atherosclerosis model is expanded, which yielded results solidifying the clinical promise of CaP@Rapa balloons. In summary, this research not only offers a more effective and reliable alternative to traditional DCB but also paves the way for further clinical trials.