Pathological analysis of local delivery of paclitaxel via a polymer-coatedstent

Background-Paclitaxel can inhibit vascular smooth muscle proliferation in v itro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal. growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been full y explored. Methods and Results-Localized drug delivery was accomplished with balloon-e xpandable stainless steel stents coated with a cross-linked biodegradable p olymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 mug of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoate d stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean n eointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 mug of paclitaxel per stent , respectively, versus CSG-coated stents without paclitaxel. However, histo logical findings suggested incomplete healing in the higher-dose (42.0 and 20.2 mug) paclitaxel-containing stents consisting of persistent intimal fib rin deposition, intraintimal hemorrhage, and increased intimal and adventit ial inflammation. Stents coated with CSG alone (without paclitaxel) had sim ilar neointimal growth as uncoated stents. In a separate group of rabbits k illed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 mug of paclitaxel Conclusions-coating appears to be a promising medium for localized drug del ivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointi mal suppression was not maintained at 90 days.