Hybrid Core–Shell Nanofibrous Scaffolds/Stents Deliver Angiotensin II Receptor Blocker to Treat Diabetic Artery Disease AITranslate

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DOI：https://doi.org/10.1021/acsapm.2c00186

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Most patients with diabetes suffer from impaired endothelial function and neointimal thickening, which contribute to arterial atherosclerosis and increase the frequency of adverse cardiovascular events. Angiotensin II receptor blockers (BIBR-277; telmisartan) exhibit distinct peroxisome proliferator–activated receptor-γ activation, which is beneficial in the treatment of arterial diseases and atherosclerosis. This investigation proposes the use of biodegradable core–shell nanofibers for the sustained and local delivery of BIBR-277 to the wall of a balloon-injured artery in the abdominal aorta of diabetic rabbits. Poly(d,l)-lactide-co-glycolide (50:50) and solutions of BIBR-277 or Dulbecco’s phosphate-buffered saline were electrospun as nanofibrous tubes and subsequently mounted on bare-metal stents. These biodegradable nanofibers released BIBR-277 for 28 days without any observable burst effect. Moreover, the drug-loaded nanofibers sustained the local delivery of BIBR-277 and increased the migration of endothelial progenitor cells in vitro while both promoting re-endothelialization and decreasing the proliferation of smooth muscle cells in vivo. In conclusion, herein, a core–shell scaffold that incorporates BIBR-277-loaded nanofibers is demonstrated to sustainably deliver cardiovascular drugs and, in doing so, provides an insight into the management of the accelerated atherosclerotic vascular disease in patients with diabetes.