Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents

Abstract

Introduction This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel. Methods To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning. Results Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels. Conclusion The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.

Taxol®: The First Microtubule Stabilizing Agent

“…The drug has been given to over a million cancer patients and also has shown promise in the treatment of neurodegenerative disease [ 73 ]. Taxol ® has been used in the preparation of stents for cardiac disease [ 74 , 75 ]. It has proven to be an indispensable tool for studies in cell biology that focus on the role of the tubulin/microtubule system in cellular functions, and also for scientists interested in microtubule structure and dynamics.…”

Aspirin Inhibits Degenerative Changes of Aneurysmal Wall in a Rat Model

“…Growing evidence indicates that aspirin can limit monocyte/ macrophage infiltration into damaged tissue by improving endothelial function and interfering with the interaction between ECs and monocyte/macrophages. In an experimental model of denuded artery, local sustained delivery of aspirin (5 and 25 lg/mm 2 ) reduced adhesion of platelet and monocyte, and promoted re-endothelialization of the injured artery [38,39]. In a rat model of neuroinflammation, chronic therapeutic doses of aspirin (10 and 100 mg/kg/day) decreased the expression of pro-inflammatory PGE2 in bacterial lipopolysaccharide-stimulated brain [18].…”

Vascular Stents Coated with Electrospun Drug-Eluting Material: Functioning in Rabbit Iliac Artery

“…DESs coated by electrospinning with biostable or biodegradable polymers able to release anti-inflammatory preparations, cytostatics, anticoagulants, ligands for endothelization, and so on have been used to restore the vascular lumen [ 17 , 23 , 28 , 47 , 49 , 50 ]. The authors of all papers note that the stents of this type are most promising healthcare products, which improve endothelialization and reduce inflammation and clotting depending on the fillers used.…”