Abstract 2483: Pharmacokinetics and Pharmacodynamics of Stent-based Delivery of Sirolimus via a Novel Metallic Anisotropic Nanoporous Surface Coating
Introduction: The vascular biocompatibility of some polymer stent surface coatings may incite greater inflammation and neointimal formation, thereby attenuating the efficacy of a stent-based therapy. The purpose of these experimental studies was to document the feasibility, arterial tissue pharmacokinetics and efficacy of a non-polymeric nanoporous surface modified sirolimus eluting stent.
Methods: Balloon expandable tubular cobalt alloy stents (VISION™, Guidant, Inc.) underwent surface modification by deposition of a thin anisotropic nanoporous cobalt alloy layer (Setagon CES™ Formulation). Twenty bare metal (BMS, n 10) and nanoporous sirolimus (25 μg/mm) eluting stents (CES™, n = 14) were implanted in the coronary arteries of 12 juvenile Yorkshire pigs. Arterial tissue pharmacokinetics and expression of PCNA were determined by HPLC or western blot analysis of samples obtained at 3, 5 and 7-days. Histological assessment was conducted at 28-days to determine dose response effects.
Results: The mean arterial sirolimus tissue concentration was 9.3 ± 1.9 ng/mg at 3-days, 1.6 ± 0.1 ng/mg at 5-days, and then 5.0 ± 5.2 ng/mg at 7-days. At 7-days, PCNA expression was significantly less for the CES™ (10.1 ± 1.4 ADU) versus BMS (16.9 ± 2.8 ADU, p = 0.03). At 28-days, the mean injury and inflammation scores were similar for the CES™ and BMS (p > 0.25). The residual fibrin deposition score was greater for the CES™ (0.7 ± 0.5) as compared with the BMS (0 ± 0.1, p = 0.0003). The mean neointimal area (1.27 ± 0.33 mm2, p = 0.01) and percent area stenosis (18.8 ± 5.1, p = 0.016) were less for the CES™ as compared with BMS (2.32 ± 1.17 mm2; 34.6 ± 18.1).
Conclusion: Stent-based delivery of sirolimus via an anisotropic metallic nanoporous surface coating inhibits neointimal formation in the porcine coronary model.