Paclitaxel coating of the luminal surface of hemodialysis grafts with effective suppression of neointimal hyperplasia

ObjectivesPaclitaxel coating of hemodialysis grafts is effective in suppressing neointimal hyperplasia in the graft and vascular anastomosis sites. However, paclitaxel can have unwanted effects on the surrounding tissues. To reduce such problems, we developed a method to coat the drug only on the luminal surface of the graft, with little loading on the outer surface.MethodsA peristaltic pump and a double-solvent (water and acetone) system were used to achieve an inner coating of paclitaxel. At the ratio of 90% acetone, paclitaxel was homogeneously coated only on the luminal surface of the graft without changing the physical properties. To determine its effect, grafts were implanted between the common carotid artery and the external jugular vein in pigs using uncoated control grafts (n = 6) and low-dose (n = 6, 0.22 μg/mm2) and high-dose (n = 6, 0.69 μg/mm2) paclitaxel inner-coated grafts. Cross-sections of graft–venous anastomoses were analyzed histomorphometrically 6 weeks after placement to measure the patency rate, percentage of luminal stenosis, and neointimal area.ResultsNo signs of infection or bacterial contamination were observed in the paclitaxel inner-coated groups. Only one of the six control grafts was patent, but all of the paclitaxel-coated grafts were patent, with little neointima. The mean ± standard error values of percentage luminal stenosis were 75.7% ± 12.7% (control), 17.5% ± 3.1% (low dose), and 19.7% ± 3.0% (high dose). The values for the neointimal area (in mm2) were 8.77 ± 1.66 (control), 3.53 ± 0.73 (lose dose), and 4.24 ± 0.99 (high dose). Compared with the control group, paclitaxel inner-coated vascular grafts significantly suppressed neointimal hyperplasia (low dose, P = .001; high dose, P = .002). Myofibroblast proliferation and migration into the graft interstices confirmed the firm attachment of the implanted graft to the surrounding tissue.ConclusionsPaclitaxel coating on the inner luminal surface of vascular grafts was effective in suppressing neointimal hyperplasia, with little inhibition of myofibroblast infiltration within the graft wall.Clinical RelevancePaclitaxel-coated vascular grafts effectively inhibited the neointimal hyperplasia of hemodialysis grafts. However, paclitaxel on the outer surface of expanded polytetrafluoroethylene grafts might prevent myofibroblast proliferation, which might cause hematomas, seromas, infections, or pseudoaneurysms in the space between the graft and surrounding tissue and result in incomplete hemodialysis needle insertion. Therefore, paclitaxel inner-coated expanded polytetrafluoroethylene grafts can reduce the coated amount of this potentially toxic drug to avoid such unwanted effects, whilst preserving its efficacy in inhibiting stenosis.