Inhibition of smooth muscle cell proliferation after local drug delivery of the antimitotic drug paclitaxel using a porous balloon catheter

Abstract

Percutaneous transluminal coronary angioplasty is an accepted treatment for coronary artery disease. The major limitation, however, is the high incidence of restenosis which limits the long-term benefit of this intervention. Paclitaxel is a new antiproliferative agent that has generated considerable scientific interest since it was introduced in clinical trials in the early 1980s. Recent in vitro studies have shown that paclitaxel has considerable antiproliferative activity in human coculture systems. In the present study the efficacy of paclitaxel was investigated after development of an intimal plaque by electrical stimulation and additional cholesterol diet and subsequent balloon angioplasty in 63 New Zealand White rabbits. Local drug delivery of paclitaxel was accomplished in 30 rabbits with a porous balloon catheter (35 holes, hole diameter 75 microm, 2.5 mm catheter diameter). Paclitaxel was administered locally with 4 ml (solution 10(-5) mol/L) using an injection pressure of 2 atm. To study the extent of restenosis and morphological changes, the animals were sacrificed 7, 28 or 56 days after intervention. After staining procedures quantification of SMC proliferation, intimal macrophages and morphological analyses were performed. Paclitaxel plasma concentrations were measured using HPLC technique. One week after balloon angioplasty the arteries treated with local paclitaxel delivery showed an insignificant trend towards a reduction in intimal smooth muscle cell proliferation (untreated 8.4 +/- 4.9 % vs paclitaxel treated 2.4 +/- 2.4 %, p = NS). However, this resulted in a significant reduction of stenosis degree of 66 % 8 weeks after intervention compared to the untreated group (untreated 41 +/- 18 % vs paclitaxel treated 14 +/- 11 %, p = 0.005). In conclusion, locally delivered paclitaxel prevented neointimal thickening in the rabbit carotid artery after balloon angioplasty. Local paclitaxel treatment may therefore be a clinical option for the prevention of restenosis after coronary interventions. However, further preclinical studies have to prove long-term efficacy and safety.

Pharmacokinetic Evaluation of Two Paclitaxel-Coated Balloons with Different Drug Load in a Short-Term Porcine Study

“…DCB are becoming a promising endovascular tool, because they have the capacity of local drug transfer to the vessel wall, inhibiting cell proliferation and moderating the hypertrophic cell response to injury [6]. An additional benefit of DCB is that they do not leave any foreign body device inside the vessel, which can produce fracture or chronic inflammation.…”

Paclitaxel‐eluting balloon: From bench to bed

“…4). Porous balloon: Oberhoff et al [43] studied the efficacy of paclitaxel using a porous balloon in carotid arteries of New Zealand White rabbits after development of an intimal plaque by electrical stimulation, cholesterol diet, and subsequent balloon angioplasty. Local drug delivery of paclitaxel (105 mol/L in 4 mL) was accomplished with a 2.5-mm long porous balloon catheter with 35 holes, (hole diameter 75 lm) using an injection pressure of 2 atm.…”

Monitoring of Gadolinium-BOPTA Uptake into the Vessel Wall during Magnetic Resonance (MR)-Guided Angioplasty of the Peripheral Arteries with a Paclitaxel/Gadolinium-BOPTA-Coated Balloon: An Experimental Study at 3 Tesla

“…Moreover, a recently published study demonstrated the MR-guided delivery of a contrast media doped solution to the vessel wall using a standard balloon catheter with multiple perforations on a 1.5 Tesla scanner [14]. Perforated balloon catheters have been described in the literature [21,22]. However, coated balloons have achieved more acceptance over the years due to more homogenous drug distribution [7,8,18].…”