Optimization of Polymeric Coatings for Vascular Balloon Deployment

Approximately 12-14% of the world’s population experiences peripheral arterial disease (PAD), a progressive atherosclerotic condition that can lead to serious complications such as ischemia, ulceration, and limb amputation if untreated. When lifestyle changes and medications fail, clinicians often use percutaneous transluminal angioplasty (PTA) —a minimally invasive procedure where a balloon, uncoated or coated with an antiproliferative drug (drug-coated balloon, DCB), is inflated at the occlusion site to restore blood flow. Although effective, restenosis and thrombosis limit PTA’s long-term success. DCBs directly address restenosis and indirectly address thrombosis by releasing an antiproliferative drug (e.g., Paclitaxel, PTX) to prevent neointimal hyperplasia and impede clot formation. Compared to uncoated balloons, DCBs improve outcomes and reduce lesion failure rates (28.6% vs 17.9%); yet, clinical efficacy remains limited by restenosis (20–45%) and thrombosis (3–10%) within six months. Moreover, commercial DCBs suffer from poor drug transfer to the vessel wall (<10%), limited retention at the target site, and short shelf life. To overcome these limitations, this work presents a customizable “off-the-shelf” hydrogel-based coating designed for patient-specific, intraoperative application to uncoated commercial balloons, enabling tailored, sustained drug delivery. The study focused on formulation optimization to achieve adequate mechanical properties, vessel adhesiveness, and prolonged PTX drug release. Calcium alginate (CA) hydrogels were generated by combining sodium alginate (SA) with calcium carbonate (CaCO&#8323;), and glucono-&#948;-lactone (GDL) was added in a fixed 1:2 GDL-to-CaCO3 molar ratio to gradually lower the pH and promote internal gelation. High and medium viscosity SA (HV, 1000-1500 mPa·s; MV, 350–500 mPa·s) were compared in terms of mechanical and coating performance; MV-SA was selected based on its easier handling and greater uniformity in coating the balloon. Five 1% MV-SA formulations with increasing concentrations of CaCO&#8323; (15–75 mM, 1X–5X) and GDL (30–150 mM) were tested, demonstrating that the 4X formulation (60 mM CaCO&#8323; and 120 mM GDL) had optimal crosslinking time (~12 min) and good mechanical stability (cross-over point: 3.21 ± 0.27%). Adding 5% polyvinyl alcohol (PVA), in a 1:1 ratio with CA, significantly enhanced mechanical stability and adhesion, as confirmed by amplitude sweep and probe tack tests. A thermal cycling protocol (&#8722;20 °C for 10 min, 55 °C for 60 min) further improved mechanical properties. FTIR confirmed hydrogen bonding between PVA and CA. As a proof of concept, PTX-loaded 4X hydrogels (0.25 mg/ml) were applied onto 3D-printed balloon phantoms (100 mm x 6 mm) mimicking a clinical scenario. Formulations with either low (13–23 kDa) or high (146–186 kDa) molecular weight (MW) PVA were tested. UV–vis spectroscopy showed that low MW PVA enabled a sustained release of 53% over 5 days, while high MW PVA led to a faster, near-complete release within 8 hours. These results confirm the versatility of the coating, as parameters such as polymer molecular weight can be adjusted. In conclusion, among the different formulations tested, the 4X + 5% low MW PVA hydrogel demonstrated favorable mechanical properties, strong adhesion, and sustained PTX release, supporting its use as a candidate coating for intraoperative application on off-the-shelf vascular balloons. This approach enables tailored drug delivery profiles aligned with patient-specific clinical needs.