Pressure-Assisted Drug Delivery Using High-Pressure Balloon Platform Improves Vascular Drug Penetration and Anti-Restenotic Effects.

High-pressure drug-coated balloon (HP@DCB) angioplasty enhances vascular drug delivery by overcoming the limitations of passive diffusion-based conventional noncompliant DCB (NC@DCB) systems. We developed a dual-layer HP balloon catheter composed of an outer Nylon 12 layer and an inner Pebax 7233 layer, and evaluated its feasibility and therapeutic efficacy as a paclitaxel (PTX)-coated platform. Shellac-based PTX coating was uniformly applied to HP@DCB and NC@DCB, and coating thickness, drug amount, release behavior, and mechanical properties were compared. Pressure-assisted drug penetration was assessed in a vascular-mimicking agarose gel phantom using fluorescent PTX and confocal microscopy. In vivo efficacy was evaluated in a balloon injury-induced rabbit iliac artery stenosis model using angiography, optical coherence tomography (OCT), histology, immunohistochemistry, and immunofluorescence examinations. Drug amount, coating thickness, and sustained drug release did not differ between groups. The mechanical robustness in HP@DCB was significantly greater than that in NC@DCB. HP@DCB produced significantly greater penetration depth and fluorescence-positive area, indicating enhanced pressure-assisted drug transfer. HP@DCB resulted in superior luminal patency, reduced neointimal hyperplasia, and favorable biological responses compared with that in NC@DCB and the sham control. These findings support DCB use based on a dual-layered HP balloon platform as a promising next-generation strategy for stenotic vascular lesion treatment.