Surface modification of endovascular stents with rosuvastatin and heparin-loaded biodegradable nanofibers by electrospinning

Abstract

Milka Janjic,1,2 Foteini Pappa,1 Varvara Karagkiozaki,1 Christakis Gitas,2 Kiriakos Ktenidis,2 Stergios Logothetidis1 1Department of Physics, Laboratory for Thin Films – Nanosystems and Nanometrology, University of Thessaloniki, 2School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: This study describes the development of drug-loaded nanofibrous scaffolds as a nanocoating for endovascular stents for the local and sustained delivery of rosuvastatin (Ros) and heparin (Hep) to injured artery walls after endovascular procedures via the electrospinning process.Purpose: The proposed hybrid covered stents can promote re-endothelialization; improve endothelial function; reduce inflammatory reaction; inhibit neointimal hyperplasia of the injured artery wall, due to well-known pleiotropic actions of Ros; and prevent adverse events such as in-stent restenosis (ISR) and stent thrombosis (ST), through the antithrombotic action of Hep.Methods: Biodegradable nanofibers were prepared by dissolving cellulose acetate (AC) and Ros in N,N-dimethylacetamide (DMAc) and acetone-based solvents. The polymeric solution was electrospun (e-spun) into drug-loaded AC nanofibers onto three different commercially available stents (Co–Cr stent, Ni–Ti stent, and stainless steel stent), resulting in nonwoven matrices of submicron-sized fibers. Accordingly, Hep solution was further used for fibrous coating onto the engineered Ros-loaded stent. The functional encapsulation of Ros and Hep drugs into polymeric scaffolds further underwent physicochemical analysis. Morphological characterization took place via scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, while scaffolds’ wettability properties were obtained by contact angle (CA) measurements.Results: The morphology of the drug-loaded AC nanofibers was smooth, with an average diameter of 200–800 nm, and after CA measurement, we concluded to the superhydrophobic nature of the engineered scaffolds. In vitro release rates of the pharmaceutical drugs were determined using a high-performance liquid chromatography assay, which showed that after the initial burst, drug release was controlled slowly by the degradation of the polymeric materials.Conclusion: These results imply that AC nanofibers encapsulated with Ros and Hep drugs have great potential in the development of endovascular grafts with anti-thrombogenic properties that can accelerate the re-endothelialization, reduce the neointimal hyperplasia and inflammatory reaction, and improve the endothelial function. Keywords: cardiovascular disease, stent, drug delivery, scaffolds, nanocoating

Keywords

• Surface modification
• endovascular stent
• rosuvastatin
• heparin
• biodegradable nanofibers
• electrospinning