Comparative analysis of biologic drug effects and distal particulate embolization among three drug-coated balloons: a histological and biological study in a rabbit model

Drug-coated balloons (DCBs) have improved clinical outcomes in femoropopliteal interventions; however, distal particulate embolization remains a critical concern, particularly in patients with chronic limb-threatening ischemia. This study aimed to histologically and biologically compare local drug effects and distal embolization among three contemporary DCBs: Ranger, IN.PACT Admiral, and Luminor. Eighteen healthy rabbits underwent descending aorta balloon angioplasty followed by DCB inflation. Animals were divided into three groups (n = 6 each): Ranger (2.0 µg/mm², 3-minute inflation), IN.PACT (3.5 µg/mm², 3-minute inflation), and Luminor (3.0 µg/mm², 1-minute inflation). At 28 days, treated aortas and downstream skeletal muscles were evaluated histopathologically and for tissue paclitaxel concentrations. In the target lesions, median paclitaxel concentrations were comparable among the Ranger, IN.PACT, and Luminor groups (3047.5, 1537.1, and 551.5 fmol/mg, respectively). Consistent with this, histological evaluations demonstrated robust and comparable medial smooth muscle cell loss across all devices. Conversely, evaluation of downstream skeletal muscles revealed striking differences in distal drug washout. Distal muscle paclitaxel concentrations were significantly higher in the Luminor group (1069.4 fmol/mg) compared to the IN.PACT (354.8 fmol/mg) and Ranger (173.8 fmol/mg) groups. Histologically, the incidence of distal particulate embolization was most severe in the Luminor group (median 4.0), followed by the IN.PACT group (3.0), both higher than the Ranger group (1.0). The low-dose Ranger DCB achieved robust drug delivery with significantly lower distal embolization risk than high-dose DCBs. These mechanistic insights may guide device selection, but clinical studies are needed to confirm limb outcomes.