Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 311 - 326
• Main Authors: Lee, Cheng-Hung, Lin, Yu-Huang, Chang, Shang-Hung, Tai, Chun-Der, Liu, Shih-Jung, Chu, Yen, Wang, Chao-Jan, Hsu, Ming-Yi, Chang, Hung, Chang, Gwo-Jyh, Hung, Kuo-Chun, Hsieh, Ming-Jer, Lin, Fen-Chiung, Hsieh, I-Chang, Wen, Ming-Shien, Huang, Yenlin
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2014; Dove Press; Dove Medical Press
• Subjects: Absorbable Implants; Acetylsalicylic acid; Animals; Aspirin; Aspirin - administration & dosage; Aspirin - chemistry; biodegradable drug-eluting nanofibers; Blood Vessel Prosthesis; Cell Adhesion - drug effects; cell adhesion to vascular stents; Complications and side effects; Dosage and administration; Drug Implants - administration & dosage; Drug Implants - chemistry; Drug-eluting stents; Endothelium, Vascular - drug effects; Endothelium, Vascular - injuries; Endothelium, Vascular - physiopathology; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - chemistry; Nanofibers - chemistry; Nanofibers - ultrastructure; Nanoparticles; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Original Research; Particle Size; Physiological aspects; Platelet Adhesiveness - drug effects; Rabbits; release characteristics; Stents; Treatment Outcome; Taiwan; biodegradable drug-eluting nanofibers; release characteristics; cell adhesion to vascular stents; acetylsalicylic acid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S51258

Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.