Rami Tzafriri, PhD. “Stent based tissue drug and binding target protein distributions: durable versus deployable coatings.”
Summary: We developed immunofluorescence (IF) methods to track drug and target protein distribution in stented arteries, to aid the development and assessment of novel stent designs. Xience Pro (74 μg Everolimus/3.0×15 mm, durable coating) and MiStent (135 μg Sirolimus/3.0×15 mm, deployable erodible coating) were implanted into porcine coronary arteries (stent-to-artery ratio ∼1.10:1) for 28, 60 or 90 days (n=9/time point). Arteries were explanted and evaluated for drug content (n=3/time point) by LC-MS/MS and for drug and mTOR distribution by IF (n=6/time point).
Both stents released the majority of drug load by 28d, but with different efficiencies (91.4±4.9% MiStent versus 21.5±1.9% Xience, P<0.001). IF showed peristrut drug localization for both stents, with similar peak intensities, but comparable interstrut intensities only at coating deployment sites.
Measurements of bulk drug release and tissue content do not reveal the complete pharmacologic impact of local drug delivery. We now have the tools to identify and track local drug distribution and response over time. Tissue deployment of zero-order dissolving crystalline drug particles is shown to temporally and spatially deliver more drug to interstrut zones that would otherwise be under-dosed without overdosing peristrut sites.
Presented at the Transcatheter Cardiovascular Therapeutics (TCT) in Denver, Colorado, Oct. 31, 2017.