title: Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan ; Department of Mechanical Engineering, Taiwan.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Mechatronics, Chang Gung University, Taiwan.
authors.forename: Yu-Huang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Mechatronics, Chang Gung University, Taiwan.
authors.forename: Chun-Der
authors.initials: CD
authors.lastname: Tai
authors.affiliation: Department of Mechanical Engineering, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Laboratory of Cardiovascular Physiology, Division of Thoracic and Cardiovascular Surgery, Taiwan.
authors.forename: Yen
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Medical Imaging and Intervention, Taiwan.
authors.forename: Chao-Jan
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging and Intervention, Taiwan.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Hsu
authors.affiliation: Hematology-Oncology Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Hung
authors.initials: H
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medicinal Sciences, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Gwo-Jyh
authors.initials: GJ
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Kuo-Chun
authors.initials: KC
authors.lastname: Hung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Fen-Chiung
authors.initials: FC
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Hsieh
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
authors.affiliation: Department of Anatomical Pathology, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.
authors.forename: Yenlin
authors.initials: Y
authors.lastname: Huang
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000737:chemistry; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010316:Particle Size; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011817:Rabbits; D015607:Stents; D016896:Treatment Outcome
chemical_list: D004343:Drug Implants; D005343:Fibrinolytic Agents; D001241:Aspirin
keywords: acetylsalicylic acid; biodegradable drug-eluting nanofibers; cell adhesion to vascular stents; release characteristics