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

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 reendothelialization 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.