Paclitaxel delivered to adventitia attenuates neointima formation without compromising re-endothelialization after angioplasty in a porcine restenosis model.

PURPOSE: To investigate the effect of paclitaxel delivered into the adventitia of pig femoral arteries on neointima formation and hyperplasia as well as re-endothelialization.
METHODS: Paclitaxel or vehicle was delivered into the adventitia of pig femoral arteries using a needle injection catheter following balloon overstretch. Arteries were then serially examined by angiography, Evan's blue staining, morphometry, and immunohistochemistry for up to 12 weeks.
RESULTS: Local adventitial delivery of paclitaxel significantly attenuated neointima formation. The area of neointima (0.41+/-0.17 versus 2.75+/-0.81 mm(2), p<0.01), the ratio of intima to media (0.12+/-0.05 versus 0.86+/-0.35, p<0.05), and the degree of stenosis (12.80%+/-3.13% versus 47.06%+/-7.25%, p<0.01) were significantly lower in the paclitaxel-treated group compared to controls. Furthermore, cell proliferation was significantly diminished following adventitial delivery of paclitaxel from day 3 to 21 compared to controls. Complete re-endothelialization was observed 3 weeks after intervention in both groups of arteries treated with paclitaxel or vehicle alone.
CONCLUSION: Paclitaxel delivered into the adventitia of pig femoral arteries effectively attenuates neointima formation after angioplasty without compromising re-endothelialization. Adventitial drug delivery may therefore be an alternative to drug-eluting stents for the prevention of restenosis.