Paclitaxel Delivered to Adventitia Attenuates Neointima Formation without Compromising Re-Endothelialization after Angioplasty in a Porcine Restenosis Model

Abstract

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 mm², 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 reendothelialization 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.

Keywords

paclitaxel restenosis neointima adventitia drug-eluting stent

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