Drug eluting stents based on Poly(ethylene carbonate): Optimization of the stent coating process

• Published in: European journal of pharmaceutics and biopharmaceutics 2012-04, Vol.80 (3), p.562-570
• Main Authors: Bege, Nadja, Steinmüller, Sven Ole, Kalinowski, Marc, Reul, Regina, Klaus, Sebastian, Petersen, Holger, Curdy, Catherine, Janek, Jürgen, Kissel, Thomas
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Biological and medical sciences; Coated Materials, Biocompatible - chemistry; Delayed-Action Preparations; DES; Diffusion; Drug Carriers - chemistry; Drug-Eluting Stents; Ethylene Oxide - chemistry; Excipients - chemistry; General pharmacology; Kinetics; Late stent thrombosis; Medical sciences; Paclitaxel; Paclitaxel - chemistry; PEC; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylenes - chemistry; Polymers - chemistry; Spray-coating; Thrombosis - chemically induced; TOF-SIMS
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.12.006

A reproducible spray-coating process for stents coated with Poly(ethylene carbonate), PEC, and Paclitaxel was developped. After expansion of the stents using a balloon catheter, confocal laser scanning micrographs of fluorescent dye loaded stents were made to demonstrate film homogeneity. The abluminal stent site was loaded more than the luminal site, which is superior for drug eluting stents. The deposition of the layers was confirmed by TOF-SIMS. The in vitro release mechanism during non-degradation conditions can be explained by diffusion-controlled drug release slightly influenced by swelling of PEC, revealing that 100% of the loaded Paclitaxel will be released via diffusion within 2 months. The PEC/Paclitaxel stent exhibits a sustained drug release, which can favorably influence the vascular biological response to the implant. First generation drug eluting stents (DES) show a fivefold higher risk of late stent thrombosis compared to bare metal stents. Therefore, new biodegradable and biocompatible polymers for stent coating are needed to reduce late stent thrombosis. In this study, a reproducible spray-coating process for stents coated with Poly(ethylene carbonate), PEC, and Paclitaxel was investigated. PEC is a biocompatible, thermoelastic polymer of high molecular weight. The surface degradation of PEC is triggered by superoxide anions produced by polymorphonuclear leukocytes and macrophages during inflammatory processes. Stents with different drug loading were reproducibly produced by a spray-coating apparatus. Confocal laser scanning micrographs of fluorescent dye loaded stents were made to investigate the film homogeneity. The abluminal stent site was loaded more than the luminal site, which is superior for DES. The deposition of the layers was confirmed by TOF-SIMS investigations. Referring to the stent surface, the drug loading is 0.32μg (±0.05) (once coated), 0.53μg (±0.11) (twice coated), or 0.73μg (±0.06) (three times coated) Paclitaxel per mm2 stent surface. The in vitro release mechanism during non-degradation conditions can be explained by diffusion-controlled drug release slightly influenced by swelling of PEC, revealing that 100% of the loaded Paclitaxel will be released via diffusion within 2months. So, the in vivo release kinetic is a combination of diffusion-controlled drug release and degradation-controlled drug release depending on the presence or absence of superoxide anions and accordingly depending on the presence or absence of