"Improvements in Drug-Coated Balloon Technologies for Peripheral Vascular Disease"

Peripheral artery disease (PAD) is a condition characterized by arterial narrowing due to atherosclerosis. It affects more than 113 million people worldwide and is associated with elevated risks of cardiovascular events and mortality. It is mainly treated with percutaneous transluminal angioplasty (PTA), a minimally invasive endovascular procedure used to restore blood flow in obstructed lower limb arteries. While commercial drug-coated balloons (DCBs) reduce lesion failure compared to uncoated balloons (28.6% vs. 17.9%), they are also associated with high rates of thrombosis (3%–10%) and restenosis (20%–45%) within 6-12 months after below-the-knee intervention. These limitations are largely attributed to inefficient drug transfer and distribution to the vessel wall. This study proposes and evaluates a method that exploits a hydrogel-based vehicle for drug coating of an off-the- shelf vascular balloon, staying within an intraprocedural window. The goal is to assess the feasibility of using a custom 3D-printed mold to apply a uniform coating that can withstand all mechanical stresses associated with PTA, including insertion into a vascular sheath and deployment under physiologically relevant conditions. The hydrogel should remain attached to the vessel wall and effectively release the drug while degrading over time. The hydrogel was formulated with 1% sodium alginate and 0–10% polyvinyl alcohol (PVA), crosslinked with calcium carbonate (30–60 mM) and glucono-δ-lactone (60–120 mM) in a 1:2 ratio, followed by thermal cycling (−20 °C for 10 min and 55 °C for 20 min) to improve mechanical properties and adhesiveness. Rheological analysis demonstrated a significant increase in adhesion energy after incorporating 5% PVA and thermal cycling, (2.798 ± 1.137 N·s vs. 17.06 ± 1.164 N·s, p= 0.000483). Functional testing was conducted using a benchtop in vitro vascular model simulating pulsatile blood flow (35 mL/min), validated using an ex vivo porcine carotid artery. Paclitaxel (0.765 mg) was incorporated into the hydrogel precursors, yielding an encapsulation efficiency of 83.55 ± 2.5%. Upon balloon deployment, the coating detached from the balloon and adhered effectively to the vessel wall, forming a continuous layer with a thickness of ~103 µm on Tygon tubing and ~294 µm on the porcine artery. The coating maintained its structural integrity throughout deployment, with no evidence of fragmentation or vessel occlusion. Drug release was monitored over a 2-hour period using UV-vis spectroscopy and over 24 -hours using high-performance liquid chromatography (HPLC), demonstrating a diffusion-driven release profile with ~30% paclitaxel retained in the coating after 24 hours. In conclusion, this work presents a drug-loaded hydrogel coating for commercial angioplasty balloons, designed for intraprocedural, on-demand applications. The system demonstrated homogeneous coating distribution, compatibility with standard endovascular procedures, and effective paclitaxel release, offering a promising platform for customizable, patient-specific treatments. Future work will explore strategies to extend drug release and integrate multi-layered coating architectures to target multiple pathways of PAD.