Complications with Coronary Stent

The introduction of stent implantation in coronary lesions had a substantial impact on improving early and late outcome compared with balloon angioplasty, providing mechanical scaffolding that reduces the impact of early elastic recoil or dissection and eliminates late lumen loss by circumferential remodeling. Implantation of coronary stents is not free of complications. In addition to wall injury at the site of stent deployment, which provides a powerful stimulus to platelet activation and thrombus formation, the surface of the stent itself constitutes a thrombogenic foreign body. Thus, without treatment, a high rate of early stent thrombosis may be expected. Furthermore, together with the impact of the arterial wall injury, a multifactorial process is initiated, leading to neointimal hyperplasia and restenosis. Restenosis is primarily attributed to neointimal hyperplasia. According to both clinical and angiographic definitions, 25-35% of successful treated atherosclerotic lesions re-occlude within 3-6 months, generating increased costs for additional revascularization procedures, atherectomy or bypass surgery.

Drug Eluting Stent (DES) and Targeted Drug Delivery

As an alternative to systemic therapy, local drug delivery offers the advantages of allowing high concentration of drug at the treatment site while minimizing systemic toxic effects. Delivering medication directly to the site of vascular injury via polymer coated stents is a rational approach to achieve adequate local drug delivery

Artificial or natural polymers that are biocompatible and biodegradable are often used for the preparation of particulate systems. Such polymers include polylactic Acid (PLA), polylactic - co-glycolic acid (PLGA), Acrylic Polymers or Co-polymers, hyaluronic acid derivatives and alginates. Among the available biodegradable polymer, the PLA and PLGA are the most widely used. Drug compounds are mixed in the polymers matrix and gradually become released as the polymer is dissolved in the tissue.

The drug polymer coating can be applied by dipping or spraying of solution, consisting of drug and polymer, mixed in desired proportion and using evaporative solvent material of relatively high vapor pressure to produce the desired viscosity and quickly established coating layer thickness. Dip coating is often undesirable for coating complex geometries like stents, since coating solution may get entrapped, in the device structure which may typically cause bridging, i.e. forming of a film across the open space between structural members of the device. This can interfere with the mechanical performance of the stent, such as expansion during deployment in a vessel lumen. Bridges tend to delaminate and rupture the coating film during expansion and provide sites that activate platelet deposition by creating flow disturbances in the adjacent hemodynamic environment. In addition delamination may cause particles to dislodge from the stent surface, potentially leading to other complications. Also multiple layer coating of drug - polymer solution is not possible with dip coating technique, as the freshly coated layer difuses within the previously coated layers causing there dissolution.

The research on developing coating technique was made at university of Texas health science centre at San Antonio, TX, USA, research and development division using stent of Sahajanand Medical Technology, India, to develop a four layer drug - polymer matrix, programmed to achieve controlled drug released and that can be spray coated by means of air suspension technique on the cardiovascular stent. Unlikethe multiple layer coating , single layer coated stents offer constant drug release profile, which is not desirable in the case of local drug delivery where drug demand decreases from the time of stent implantation.

To ensure the proper coating integrity stents were subjected to balloon expandability test. Drug coated stents were crimped on the balloon by means of crimping machine. The crimped stents were expanded by expansion device. Sterile fluid was pumped as an expansion media. Stent was crimped on the balloon and expanded at rated pressure of 6 atm.

High performance Liquid Chromatography (HPLC) established the efficiency of modified air suspension coating technique and controlled release of paclitaxel drug from four layer coated stent.

Modified Air Suspension Technique

In the recent research in testing modified air suspension technique by university of Texas Health Science Centre of SAN Antonio, a decrease in drcplet size was observed when the atomizing pressure was increased with the help of modified air suspension technique.

Increase in droplet size can cause non-uniform surface, which is not desirable for small implantable medical devices like cardiovascular stents as these surfaces could be highly thrombogenic. By using modified air suspension technique a decrease in droplet size was observed when the atomizing pressure was increased.

Scanning Electron microscopy (SEM) revealed a consistent coating profile devoid of any irregularities like cracking and delamination after crimping and expansion of stent. This demonstrates that coating film is elastic enough to withstand the expansion mechanism. With no crack formation on the coating film, at the mechanically stressed sites of the stent, SEM analysis revealed complete adhesion of the film.

A sharp scalpel was used for scratching the coated layer from the stent surface and the thickness was measured using scanning electron microscope (SEM) which indicates the uniform coating thickness along the entire surface of the stents. The uniform coating thickness can be attributed to the rotating motion of the stent on its axis and oscillating motion of the spray nozzle which creates the wide spray pattern allowing the atomized droplets to access entire surface of the stent. High performance liquid chromatographic exhibited consistency in drug content on the stent surface showing reproducibility and accuracy of the modified air suspension coating technique.

(Abstracted from an article by Ankur Raval, Animesh Choubey, Chhaya Engineer, Haresh Kotadia and Devesh Kothwala, published in , "Trends Biomaterial Artificial Organs, Vol 20(2)", which describes the modified air suspension technique for coating the coronary stent with paclitaxel drug and biodegradable polymeric blends.)