Bioresorbable Coronary Stents Containing Drugs for
Prevention of Restenosis

Dr. Meital Zilberman,
Dept. of Biomedical Engineering, Faculty of Enginering Tel-Aviv University

Summary of Research Activities
Metal coronary stents are used to stabilize dissections, eliminate vessel recoil and guide remodeling after balloon angioplasty. The rationale for a bioresorbable stent is support of the arterial wall only during vessel healing, long term delivery of drug to the vessel wall from an internal reservoir and no need for a second surgery to remove the device. In a previous study we developed and studied a novel expandable bioresorbable coronary stent. The design is based on Poly(L-lactic acid) fibers. The current research focuses on development of methods for incorporation of anti-proliferative drugs for restenosis prevention in the stent. The fiber-based stent degrades with time to non-toxic substances. Hence, degradation of the polymer and diffusion processes enable effective controlled release of the drug molecules from the stent to the blood vessel wall. Incorporation of the drug molecules to the fibers should be done without affecting the stent mechanical properties or the drug's activity. Therefore bioresorbable coatings that contain the drug are being developed and bonded to the bioresorbable fibers and fiber-based stents. This research project also includes an in-vitro study of fiber degradation and drug controlled release mechanism from it. It should be emphasized that drug eluting bioresorbable expandable coronary stent has not been developed yet.

Bioresorbable fibers were made from a relatively high molecular weight PLLA (RESOMERTM L21, Boehringer Ingelheim, Germany) with inherent viscosity = 3.6 dL/g in CHCl3 at 30oC . This polymer was melt spun at 190oC and drawn at 80oC to a drawing ratio of 8:1, to create a fiber with the following mechanical properties in tension: ultimate strength: 974 MPa, young’s modulus: 4.9 Gpa, maximal strain: 0.88. This fiber combines high strength and modulus with good ductility and flexibility. A novel expandable stent (15 mm length, 3.0 mm final (dilated) diameter and 1.8 mm pre-dilated diameter) was developed from these PLLA fibers, in a previous study.

Anti-proliferative drugs, can combat restenosis by inhibiting vessel smooth muscle cell proliferation. Bioresorbable “coatings” that contain two types of drugs (water soluble, such as sirolimus, and non-water soluble, such as paclitaxel) are being developed and studied by us. Since these drugs are expensive, The primary study was carried out using less expensive molecules that can be used as a model.

Four types of 75/25 poly(DL-lactide - co - glycolide) (PDLGA) microspheres containing Albumin (water soluble) were prepared through the double emulsion process. In general, these 10-70 mm microspheres have smooth surface and a core/shell (aqueous phase / polymer) structure. Most of the Albumin used was encapsulated in the microspheres (85 % average). The microspheres were bound to the PLLA fibers, i.e., served as a coating. The cumulative Albumin release profiles from the four types of microsphere-loaded fibers are presented in Fig. 1. In general, a burst effect is accompanied by linear cumulative release profile, as expected for a “reservoir” system, such as these core/shell microspheres. These results indicate that the microspheric reservoirs enable effective protein release from fibers. The release profile can be tailored and is determined by the initial molecular weight of the bioresorbable polymer and its degradation rate. The "burst" effect can be controlled by choosing the right processing conditions and by controlling the microsphere shell thickness.

The study of fibers loaded with microspheres that contain paclitaxel and multi-reservoir systems (see Fig. 2) is in progress.

Fig. 1: In-vitro cumulative Albumin release from 75/25 PDLGA microsphere-loaded fibers
Fig. 2: A multi-reservoir microsphere