Differences in Pharmacokinetic and Histopathological Effects of Five Drug-Coated Balloons: An Experimental Study in Rabbit

Background: The optimal design concept and the safety of drug-coated balloons (DCBs) have not been completely determined yet. Also, the optimal approach for DCB-based revascularization of peripheral artery diseases still remains undefined. This study was designed to explore the in vivo pharmacokinetic and histopathological effects of DCBs using Ranger and 4 Chinese DCBs after implantation and administration in New Zealand rabbits. Materials and Methods: Fifty New Zealand rabbits were divided into 5 groups with 10 rabbits in each group according to the DCB used: Ranger (Boston Scientific), Orchid (Acotec), Reewarm (Endovastec), Ultrafree (Zylox), and Yaohang (Polyrey). After being guided to the lower segment of the abdominal aorta, the DCB was inflated for 3 minutes. Plasma, inflated infrarenal aorta, vastus lateralis muscle, anterior tibial muscle, and right toes were harvested for histological and paclitaxel concentration analyses 4 hours or 28 days after the angioplasty. Results: At 4 hours after aortic angioplasty, the overall paclitaxel concentrations in aortic wall were not statistically different (p = 0.050), but the paclitaxel concentrations in vastus lateralis muscle (p = 0.002), anterior tibial muscle (p = 0.006) and toe (p < 0.001) were not totally same according to the results of Kruskal-Wallis test. In toe, concentrations of paclitaxel were significantly lower for the Ranger (120.8 ng/g) DCB than for the Orchid (1880 ng/g; p = 0.008), Reewarm (347 ng/g; p = 0.016), and Ultrafree (261 ng/g; p = 0.016) DCBs. Concentrations of paclitaxel in the toe were not statistically different between Ranger and Yaohang DCBs (p = 0.421). Neointimal area (p < 0.001), neointimal thickness (p < 0.001), and percentage of luminal stenosis (p < 0.001) were less for Ranger DCB than for other DCBs 28 days after aortic angioplasty. The differences in paclitaxel concentrations in tissues 28 days after aortic angioplasty were not statistically significant. Conclusion: Different design concepts will make a difference in the in vivo pharmacokinetic and histopathological effects of DCBs. The Ranger DCB can achieve similar drug delivery efficiency as other higher-dose DCBs and fewer neointimal hyperplasia. Although clinical implications remain to be further investigated, the present results may provide implications for the design and use of DCBs. Clinical Impact The current preclinical study suggested that different design concepts would make a difference in the pharmacokinetic and histopathological effects of drug-coated balloons (DCBs). Though Ranger DCB had the lowest paclitaxel loading in this study, it still achieved similar drug delivery efficiency with other higher-dose DCBs. Also, neointimal hyperplasia was less for the Ranger DCB than for the other DCBs 28 days after aortic angioplasty. Although clinical implications remain to be further investigated, the present results may provide implications for the design and use of DCBs.