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


METHODS
A 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/mm(2)) and high-dose (n = 6, 0.69 μg/mm(2)) 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.


RESULTS
No 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 mm(2)) 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.


CONCLUSIONS
Paclitaxel 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.
Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
Insu
I
Baek
Cheng Zhe
CZ
Bai
Jinsun
J
Hwang
Hye Yeong
HY
Nam
Jong-Sang
JS
Park
Dae Joong
DJ
Kim
D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000737:chemistry; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia; D007601:Jugular Veins / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011474:Prosthesis Design; D006435:Renal Dialysis; D012995:Solubility; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D014654:Vascular Patency / Q000187:drug effects
D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D017239:Paclitaxel