Safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon following bare metal stent implantation in rabbit aorta abdominalis

Abstract

Background: Drug-eluting balloons (DEB) may be promising technology for treating atherosclerotic arterial disease. In fact, several DEBs have been clinically available for the treatment of coronary in-stent restenosis (ISR), de novo coronary lesions, and peripheral artery disease.

Objective: We sought to elucidate the mechanism of action and in vivo safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon.

Methods: In vitro cytotoxicity of a novel DEB on human umbilical vein endothelial cells (HUVECs) and in vivo pharmacokinetics of DEB in a rabbit aorta abdominalis were assessed. Then, bare metal stents (BMS) were implanted at both the proximal and distal sites of the rabbit aorta abdominalis. Stented vascular segments were immediately dilated with a bare balloon (control group) or the DEB (DEB group) randomly. Histological evaluation was performed in all treated segments at 28 days. Because paclitaxel is a tubulin-disrupting agent that binds preferentially to β-tubulin, we measured β-tubulin expression in aortal stent specimens via immunohistochemistry.

Results: We observed that DEB was compatible and could reduce neointimal hyperplasia compared with the bare balloon. Meanwhile, immunohistochemistry revealed that β-tubulin expression in the DEB group increased compared with the control group, indirectly suggesting successful uptake of paclitaxel by vessel walls after DEB dilation.

Conclusions: The novel DEB is safe and has a favorable vascular healing response on neointimal hyperplasia.

Keywords: Neointimal hyperplasia; paclitaxel-eluting balloon; pharmacokinetics.

Fig. 1.

WST-1 assay indicates human umbilical vein endothelial cell (HUVEC) viability after co-incubation with iopromide-coated balloon or bare balloon up to 48 h. Data are expressed as means ± SD of six independent experiments (ratio on control 1). ^∗$\mathit{P}\mathrm{<}0.05$ vs. control group.

Fig. 2.

Paclitaxel release kinetics of DEB in vivo.

Fig. 3.

Representative images of aorta abdominalis assessed by angiography immediately after BMS implantation (arrowhead: BMS implantation sites). (Colors are visible in the online version of the article; http://dx.doi.org/10.3233/BME-151551.)

Fig. 4.

Representative histological images at low-magnification (100x, upper image) and high power magnification (200x, lower image) 28 days after balloon treatment. DEB could inhibit neointimal hyperplasia in contrast with control. Sections shown are stained with hematoxylin and eosin (H&E). (Colors are visible in the online version of the article; http://dx.doi.org/10.3233/BME-151551.)

Fig. 5.

β-tubulin expression in stented vascular vessels was measured via immunohistochemistry. Quantitative measurement of immunohistochemical images as a ratio of β-tubulin-positive cells indicated that β-tubulin expression was induced in the DEB group (arrowhead). All values are given as means ± SD. ∗ significantly different compared to the control group ($\mathit{P}\mathrm{<}0.05$). (Colors are visible in the online version of the article; http://dx.doi.org/10.3233/BME-151551.)