Composite Fiber Structures Loaded with Paclitaxel Used in Coronary Stents

Dr. Meital Zilberman, Department of Biomedical Engineering,
Tel-Aviv University

Summary of Research Activities

The development of metal vascular stents with drug eluting coatings is considered as a major advancement in treatment of coronary artery disease. These stents dramatically reduce the incidence of in stent restenosis. In one of our recent studies bioresorbable stents were developed and their mechanical properties and degradation characteristics were studied.

The current research activity focuses on novel bioresorbable porous structures loaded with paclitaxel. This system is designed to be used as a coating for the carrying core fiber of the stent. The resulting novel core/shell fiber structures are designed to combine good mechanical properties together with desired paclitaxel controlled release profiles for treatment of Restenosis. Thus, a stent based on such fibers will combine mechanical support together with paclitaxel controlled release into the blood vessel wall, for prevention of restenosis.

The coating technique utilizes the freeze drying of "water in oil" emulsion where the emulsion's organic phase consists the paclitaxel molecules. The effect of the emulsion's composition and processing parameters on the coating’s microstructure and on the resulting paclitaxel controlled release profile were extensively studied. The microstructure of the coating (“shell”) was studied using scanning electron microscopy and the in-vitro drug release from the fibers was studied for three months using HPLC analysis for determining the drug contents within the release medium.

The results show that all release profiles exhibited diffusion-controlled pattern and all released quantities are in the therapeutic range. The shell's structure and the resulting taxol release profile are affected mainly by the drug and polymer contents, emulsion's aqueous:organic phase ratio and stirring rate. Higher taxol content resulted in higher drug release. Higher stirring rate resulted in higher drug release, due to lower pore size which enables better penetration of water to the polymer domains. The composite fibers combine relatively high tensile strength together with good ductility and flexibility.

We have demonstrated that proper selection of processing conditions, based on kinetics and thermodynamic considerations, can yield core/shell fiber structures with desired mechanical properties and paclitaxel release behavior.

Fig. 1: A schematic representation showing the concept of composite core/shell fiber structures loaded with paclitaxel, designed to be used as basic elements of bioresorbable vascular stents.