Towards Stents with Drug-Eluting Tethered Polymers

Clemson University, Clemson SC

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Coronary artery disease is the single leading cause of death in the United States, and drug-eluting stents (DES) have been developed as a means to open blocked or occluded arteries to significantly improve blood flow and provide controlled drug release to minimize the body's reaction to the stent. Our long-term goal is to develop durable, drug-releasing nano-coatings that cannot be compromised during stent handling and insertion. The specific hypothesis is that crack- resistance polymer nanolayers can be grafted from a stent surface. The nanolayers provide carefully chosen chemical functional groups to which a clinically relevant amount of drug could be immobilized and then released over time once the stent is inserted into a stenotic artery. Our rationale for this study is that conventional DES polymer coatings 1) may crack during stent expansion; 2) cause some patients to have adverse reactions; and 3) require the polymer and drug to be miscible in a common solvent during the coating process, which limits the number of available drugs that can be used. Therefore, the emphasis of this proposed research is on the synthesis of durable nano-coatings and the characterization of release profiles of clinically relevant drugs (e.g., paclitaxel, rapamycin). [unreadable] [unreadable] The specific aims are to: 1. Demonstrate the surface-grafting of drug-containing polymer chains from stents We will use graft polymerization to grow polymer nanolayers from specially designed functional groups that attach covalently to stent surfaces. After polymerization, the side chains of the polymer will be reacted with clinically relevant drugs, and we will correlate the efficacy of drug attachment with polymer layer thickness and grafting density. 2. Evaluate drug elution from the tethered chains We will monitor the drug-elution characteristics under physiologic conditions using a microarray-based spectroscopic imaging technique. The time-dependent amount of drug released will be characterized as a function of polymer layer thickness and grafting density as well as the type of drug molecule. We will also investigate the use of biocompatible overlayers to control hydrolysis and diffusion rates. NARRATIVE [unreadable] [unreadable] Developments in drug-eluting stents (DES) would reduce the rate of revascularization and improve patient recovery using a procedure much less invasive and costly than coronary artery bypass grafting. Improved DES technology also expands the potential use to those cases that are currently less amenable to DES such as multivessel disease, especially for diabetic patients who represent a growing segment of our population. [unreadable] [unreadable] [unreadable]