Controlled delivery of paclitaxel from stent coatings using novel styrene maleic anhydride copolymer formulations.

ABSTRACT

The controlled release of paclitaxel (PTx) from stent coatings comprising an elastomeric polymer blended with a styrene maleic anhydride (SMA) copolymer is described. The coated stents were characterized for morphology by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and for drug release using high-performance liquid chromatography (HPLC). Differential scanning calorimetry (DSC) was used to measure the extent of interaction between the PTx and polymers in the formulation. Coronary stents were coated with blends of poly(b-styrene-b-isobutylene-b-styrene) (SIBS) and SMA containing 7% or 14% maleic anhydride (MA) by weight. SEM examination of the stents showed that the coating did not crack or delaminate either before or after stent expansion. Examination of the coating surface via AFM after elution of the drug indicated that PTx resides primarily in the SMA phase and provided information about the mechanism of PTx release. The addition of SMA altered the release profile of PTx from the base elastomer coatings. In addition, the presence of the SMA enabled tunable release of PTx from the elastomeric stent coatings, while preserving mechanical properties. Thermal analysis reveled no shift in the glass transition temperatures for any of the polymers at all drug loadings studied, indicating that the PTx is not miscible with any component of the polymer blend. An in vivo evaluation indicated that biocompatibility and vascular response results for SMA/SIBS-coated stents (without PTx) are similar to results for SIBS-only-coated and bare stainless steel control stents when implanted in the non-injured coronary arteries of common swine for 30 and 90 days.