Abstract 18836: Drug Delivery Strategies Employing Angioplasty Balloons for Treatment of Atherosclerosis

Introduction: Conventional treatments of atherosclerosis including angioplasty and stenting have adverse drawbacks like restenosis and thrombosis. Recent research on drug eluting balloons show that anti-restenotic drugs delivered at the atherosclerotic lesion via angioplasty balloons are eliminated through circulation. Our goal is therefore to provide a sustained and targeted drug release at the diseased site via paclitaxel loaded Urethane doped polyester (UPE) nanoparticles (NPs) eluting balloons. Materials and Methods: Paclitaxel-loaded UPE NPs were fabricated and characterized by dynamic light scattering, SEM and TEM. These nanoparticles were coated onto the balloon surface by either Layer by Layer (LbL) electrostatic or hydrogel (acrylic acid) coatings. NP loading was optimized by studying various parameters like incubation saturation and coating efficiency. SEM micrographs were acquired to visualize the coatings and the loaded nanoparticles. Finally, rat arteries were harvested and NP delivery via angioplasty balloons to the arterial lumen ex vivo was investigated. Results and Discussion: UPE NPs had an average size of 300 nm and zeta potential of -28.5 mV. NP loading reached saturation at 24h and 16h, allowing over 65% and 80% of UPE NPs to be loaded for LbL and hydrogel, respectively. Moreover, ex vivo NP retention results revealed that a higher rate of NPs can be delivered to the arterial wall by the hydrogel coating compared to LbL coating. It was also noted that coating materials (LbL and hydrogel coating) and UPE NPs were non-toxic to human vascular endothelial cells. Conclusion: Our results conclude that LbL nanoparticle loading, although considered as a well-established procedure, provides a comparatively low loading efficiency and NP transfer than that obtained by the hydrogel technique. However, it is difficult to obtain a uniform hydrogel coating consisting of NPs on the balloon surface. If successful, these techniques can provide a means for delivering drug loaded nanoparticles to the atherosclerotic lesion locally.