Abstract
Paclitaxel (PTX) has been recognized as a promising drug for intervention of vascular reconstructions. However, it is still difficult to achieve local drug delivery in a spatio-temporally controllable manner under real-time image guidance. Here, we introduce an ultrasound (US) triggered image-guided drug delivery approach to inhibit vascular reconstruction via paclitaxel (PTX)-loaded microbubbles (PLM) in a rabbit iliac balloon injury model. PLM was prepared through encapsulating PTX in the shell of lipid microbubbles via film hydration and mechanical vibration technique. Our results showed PLM could effectively deliver PTX when exposed to US irradiation and result in significantly lower viability of vascular smooth muscle cells. Ultrasonographic examinations revealed the US signals from PLM in the iliac artery were greatly increased after intravenous administration of PLM, making it possible to identify the restenosis regions of iliac artery. The in vivo anti-restenosis experiments with PLM and US greatly inhibited neointimal hyperplasia at the injured site, showing an increased lumen area and reduced the ratio of intima area and the media area (I/M ratio). No obvious functional damages to liver and kidney were observed for those animals. Our study provided a promising approach to realize US triggered image-guided PTX delivery for therapeutic applications against iliac restenosis.
Highlights
Local delivery of PTX through injection catheters, balloon catheters and coated balloons has developed[12,13]
PTX-loaded MBs (PLM) was prepared by thin-film rehydration and mechanical vibration method through the following several steps, film-forming, solvent evaporation, hydration, gas displacement and mechanical vibration (Fig. 1A)
The stability test including PLM concentrations, bubble size and drug leakage revealed there were gradually decreased bubble concentrations and increased bubble size when PLM were left to stand for a period of time (0.5 h to 32 h) (Fig. 1E,F)
Summary
Local delivery of PTX through injection catheters, balloon catheters and coated balloons has developed[12,13]. Drug-eluting techniques (DES), such as balloons and stents covered with PTX, have shown promising progress in decreasing restenosis and revascularization rates[14,15]. Studies have revealed a possible increase in the rate of stent thrombosis with DES due to decreased endothelialization of stented regions[16,17]. The polymer coating on DESs may induce inflammatory responses that could induce stent thrombosis[18]. These limitations have prompted us to search for other local drug delivery modalities to inhibit restenosis and to avoid systemic adverse effects. We prepared the PTX-loaded MBs (PLM) and investigated the efficacy of PLM combined with US against restenosis in rabbit iliac balloon injury model. The functional damages to liver and kidney of these animals were demonstrated
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