AUTHOR=Akers Nicole M. , Dugas Tammy R. TITLE=Peripheral artery disease and local drug delivery: a review of disease pathology and drug delivery systems for therapy below the knee JOURNAL=Experimental Biology and Medicine VOLUME=Volume 250 - 2025 YEAR=2025 URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10754 DOI=10.3389/ebm.2025.10754 ISSN=1535-3699 ABSTRACT=Peripheral artery disease (PAD) is a disease of both atherosclerotic and thromboembolic pathology, affecting more than 230 million people globally. PAD patients are at an increased risk of thrombotic events and often require lifelong antithrombotic therapy. Thromboembolism can lead to complete occlusion of affected arteries and put patients at risk for critical limb threatening ischemia (CTLI). PAD blockages are cleared using drug-eluting stents (DES) and drug-coated balloons (DCB). However, PAD treatment below the knee (BTK) presents unique challenges. While DCB are frequently used to treat BTK disease, no DCB has gained FDA approval for this indication. However, innovation in the field has produced drug delivery systems and formulations that may yet enhance the effectiveness of these therapies. In this review, we will provide a brief overview of the pathological mechanisms associated with PAD and review the materials and drugs frequently used in DCBs with an emphasis on excipients and drug carriers. Finally, we will highlight emerging devices undergoing clinical trials to treat BTK disease and how they differ from their predecessors.