Nanocopoeia (United States)

Restenosis is an adverse outcome of angioplasty characterized by re-narrowing of the arterial lumen. Current generation drug-eluting stents (DES) used to treat restenosis are associated with unintended complications, including potentially fatal late-term thrombosis due to delayed reendothelialization. Our research aimed to incorporate two red wine polyphenols, resveratrol (RESV) and quercetin (QUER), into a novel coating for DES. In vitro evaluation of poly(styrene-isobutylene) tri-block polymer loaded with synergistic combinations of RESV:QUER revealed that the films release drug at therapeutic levels, significantly inhibiting VSMC proliferation and macrophage and platelet activation. In vitro, we observed that RESV promoted endothelial cell migration and proliferation under laminar shear stress. Thus, we hypothesized that miniature stents eluting RESV and QUER would both inhibit restenosis and promote reendothelialization after stenting injury. To test this hypothesis, we utilized a rat model of carotid artery stenting. Local delivery of RESV and QUER from a stent platform dose-dependently blocked restenosis and local inflammation 28 days after stenting compared with bare metal stents (BMS). Additionally, we found that these compounds accelerated reendothelialization compared with BMS. This suggests that RESV and QUER may have utility as therapeutics in a novel coating for DES.

Abstract Poly(styrene‐b‐isobutylene‐b‐styrene) (SIBS) block copolymer, a thermoplastic elastomer, is used in clinical practice as the drug‐eluting polymeric coating on the Taxus® coronary stent. We have been developing new architectures comprising an arborescent arbPIB core synthesized by inimer‐type living carbocationic polymerization of isobutylene (IB) by the 4‐(2‐methoxy‐isopropyl)styrene and 4‐(1,2‐oxirane‐isopropyl)styrene inimers in conjunction with TiCl4, from which polystyrene is blocked (D_SIBS). These novel self‐assembling “double” networks have unique properties. ElectroNanospray™, a proprietary technology developed at the University of Minnesota, was used to coat coronary stents with selected D_SIBS polymers loaded with Dexamethasone, a model drug. This paper will demonstrate how drug release profiles can be influenced by both the molecular weight of the DIB midblock and spraying conditions of the polymer‐drug mixture.

This paper reviews the development of coronary stents from a polymer scientist's view point, and presents the first results of an interdisciplinary team assembled for the development of new stent systems. Poly(styrene-b-isobutylene-b-styrene) block copolymer (SIBS), a nanostructured thermoplastic elastomer, is used in clinical practice as the drug-eluting polymeric coating on the Taxus coronary stent (trademark of Boston Scientific Co.). Our group has been developing new architectures comprising of arborescent (dendritic) polyisobutylene cores (D_SIBS), which were shown to be as biocompatible as SIBS. ElectroNanospray (Nanocopoeia Inc.) was used to coat test coupons and coronary stents with selected D(S)IBS polymers loaded with dexamethasone, a model drug. The surface topology varied from smooth to nanosized particulate coating. This paper will demonstrate how drug release profiles were influenced by both the molecular weight of the polyisobutylene core and spraying conditions of the polymer-drug mixture.