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.

Macromolecular Engineering and Additive Manufacturing of Poly(styrene-b-isobutylene-b-styrene)

“…SIBS blends with other polymers have been studied for different applications. For example, SIBS blended with the styrene maleic anhydride (SMA) copolymer was studied for drug-eluting stent coatings . Morphological studies showed that SMA formed a separate phase due to immiscibility with SIBS.…”

“…For example, SIBS blended with the styrene maleic anhydride (SMA) copolymer was studied for drug-eluting stent coatings. 33 Morphological studies showed that SMA formed a separate phase due to immiscibility with SIBS. In another report, 34 SIBS was blended with poly-(ethylene glycol), and the blends were electrospun into elastic fiber mats for drug release application.…”

Diffusion-Controlled Quasi-Stationary Mass Transfer for an Isolated Spherical Particle in an Unbounded Medium

“…For the diffusion-controlled quasi-stationary process, a mathematically complete set of the exact analytical solutions is obtained in implicit forms for consideration of both dissolution of a particle in a solvent and growth of it by precipitation in a supersaturated environment. Understanding the dissolution behavior of solid particles in liquid plays an important role in pharmaceutical dosage form development (Chen and Wang, 1989;Rice and Do, 2006), and particle growth by precipitation in a supersaturated environment is relevant to the drug-polymer microsphere formation process (Wu, 1995) as well as the observed phase separation process during solvent removal in drying of a coating with the drug-polymer mixture (Barocas et al, 2009;Richard et al, 2009). The commonly used explicit formula based on the solution with quasi-steady-state approximation is shown to provide unsatisfactory accuracy unless the solubility is restricted to very small values (corresponding to < 10 −4 ).…”

Surface Modifications of Medical Grade Stainless Steel

“…In a study, PoP-coated stents showed severe histiolymphocytic and fibromuscular reactions resembling a foreign body reaction [183]. In another study, the controlled release of Px from the stent coating of an elastomeric polymer mixed with styrene-maleic anhydride (SMA) copolymer demonstrated that Px was compatible with any component of the polymer blend [184]. A native endothelial extracellular matrix mimicking a self-assembled nanofibrous matrix was described as a new treatment model.…”