Liquid Drug Delivery Approaches for the Treatment of Occlusive Arterial Disease: A Systematic Review

Objective: Local Liquid drug (LLD) delivery devices have recently emerged as a novel approach to treat peripheral arterial disease. This systemic review aims to identify and evaluate the clinical utility of the most commonly used delivery devices. Methods: A systemic review was performed using the Medical Subjects Heading terms of "drug delivery," "liquid," "local," and "cardiovascular disease" in PubMed, Google Scholar, and Scopus. Results: Four commonly used delivery devices were identified, including (1) the Bullfrog Micro-Infusion Device, (2) the ClearWay RX Catheter, (3) the Occlusion Perfusion Catheter, and (4) the Targeted Adjustable Pharmaceutical Administration. All have shown to successfully deliver liquid therapeutic into the target lesion and have exhibited favorable safety and efficacy profiles in preclinical and clinical trials. The LLD devices have the ability to treat very long or multiple lesions with a single device, providing a more economical option. The safety profile in LLD clinical studies is also favorable in view of recent concerns regarding adverse events with crystalline-paclitaxel-coated devices. Conclusion: There is clear clinical evidence to support the concept of local liquid delivery to treat occlusive arterial disease. Clinical Impact The 'leave nothing behind' strategy has been at the forefront of the most recent innovations in the field of interventional cardiology and vascular interventions. Although drug coated balloons have overcome limitations associated with plain old balloon angioplasty and peripheral stents, recent safety concerns and cost considerations have impacted their usage. In this review, various liquid drug delivery devices are presented, showcasing their capabilities and success in both preclinical and clinical settings. These innovative liquid delivery devices, capable of targeted delivery and their ability to be re-used for multiple treatment sites, may provide solutions for current unmet clinical needs.