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.

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“…PCL is a biocompatible and biodegradable material [ 53 ]. The use of biodegradable polymers loaded with ASA was reported to be highly successful in both: prevent platelet adhesion and promote the endothelialization of biomaterials using an animal model (rabbit) [ 61 ].…”

“…Several studies have confirmed that a decrease in the extracellular pH led to cell apoptosis [ 70 ]. However, previous studies have shown that similar ASA release profiles have no significant effect on the cell cytocompatibility in vivo since the local acidification is mitigated due to the larger blood volume in the implantation site [ 61 , 71 ].…”

Poly(styrenesulfonate)-Modified Ni–Ti Layered Double Hydroxide Film: A Smart Drug-Eluting Platform

“…Poly(lactic-co-glycolic acid) was the mostly used biodegradable material. 12,13 Through adjustment of the ratio of poly(lactic acid) and poly(glycolic acid), the drug release kinetics can be controlled. A lot of drugs and biomolecules have been successfully loaded using this material, including DNA molecules, curcumin, sirolimus, emodin, and so on.…”

“…Recently, a lot of researches have focused on the biodegradable polymer drug-loading layer. Poly­(lactic- co -glycolic acid) was the mostly used biodegradable material. , Through adjustment of the ratio of poly­(lactic acid) and poly­(glycolic acid), the drug release kinetics can be controlled. A lot of drugs and biomolecules have been successfully loaded using this material, including DNA molecules, curcumin, sirolimus, emodin, and so on. − Some other biodegradable polymers were also investigated, such as poly­(ethylenimine) .…”