Layer-by-layer assembly for making drug-eluting stents

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DESCRIPTION (provided by applicant): The drug-eluting stent (DES) is known to be the third revolution in Interventional Cardiology. While drug delivery from stents has resulted in substantial improvement in prevention of restenosis, the types of drugs to be delivered and the desired release kinetics are not well understood. The DES field is still in its infant stage, and it requires development of better stents with more desirable drug release kinetics. It is critical to obtain the ability to control the drug release kinetics from stents and to understand the local concentrations of the released drug in relation to the strut spacing of a stent. The objective of this project is to develop novel drug coating methods based on the layer-by-layer (LBL) assembly technology, in conjunction with well-established polymer coating methods. Paclitaxel is used as the model drug in the LBL approach. Only several layers will be necessary for LBL assembly on the stents. This project is based on the hypothesis that different regions of a stent should have different drug release profiles based on the density of struts on the stent to obtain homogeneous local paclitaxel concentration in the tissue surrounding the stent. The specific aims of this project are: (1) to prepare paclitaxel-loaded LBL assembly blocks (paclitaxel microparticles and paclitaxel-loaded polymer microspheres); (2) to build drug-eluting layers on substrates (stainless steel wires, plates, and stents) using combination of LBL assembly and microfabrication; (3) to examine the three-dimensional (3-D) distribution of the drug inside the LBL assemblies as a function of time, and to examine the drug release profiles; and (4) to modify the assembled building blocks with heparin for improved biocompatibility and to examine its effect on drug release profiles. The significance of this project is that the drug coating methods based on LBL assembly and microfabrication can provide tools for researchers to load drugs with the ability to control the local drug release profiles along the stent. The ability to obtain homogeneous local drug concentration in the tissue surrounding the stent will be essential in finding the right drugs and their optimum release kinetics as more and more new drugs and new stent designs will be developed for the prevention of restenosis.