Abstract
OBJECTIVE: Peripheral artery disease is the second most common cardiovascular disease. It can often occur in complex form when there is a presence of long, diffuse, and multiple lesions. Current treatments use either single long drug-coated balloons (DCBs) or multiple DCBs; however, treatment success is limited. The purpose of this study was to investigate the preclinical feasibility of our multiple-release Tailored Medical Devices DCB (MR-TMD-DCB) to treat multiple arterial segments using a single DCB. METHODS: The MR-TMD-DCBs were developed using a two-layer coating approach. The DCBs were developed in a certified Current Good Manufacturing Practices facility using presterilized materials and reagent and then characterized for coating morphology, thermal and chemical changes, and in vitro particulate shedding. The drug loss, tissue uptake, and undelivered drug amounts were analyzed using an in vitro peripheral artery flow model and explanted pig arteries. Then, an in vivo survival study was performed using a healthy porcine model to measure the short-term drug uptake (seven swine; 14 treatments at day 1) and retention (seven swine; 14 treatments at day 7) in two different arterial segments after treatment with a single MR-TMD-DCB. RESULTS: The coating on the MR-TMD-DCB was smooth and homogeneous with paclitaxel molecularly dispersed in its amorphous state. A negligible number of particulates were shed from the MR-TMD-DCB coating. A similar amount of drug was accurately delivered into two separate explanted arteries using a single MR-TMD-DCB during the in vitro flow model testing (707 ± 109 ng/mg in the first explanted artery and 783 ± 306 ng/mg in the second explanted artery). The MR-TMD-DCB treatment resulted in equivalent drug amounts in the two arterial segments at day 1 (63 ± 19 ng/mg in the first treatment site and 59 ±19 ng/mg in the second treatment site) and at day 7 (9 ± 6 ng/mg in the first treatment site and 10 ± 6 ng/mg in the second treatment site). In addition, the drug levels at each time point were in the clinically relevant range to prevent neointimal hyperplasia. CONCLUSIONS: The MR-TMD-DCBs provided equivalent and clinically relevant drug retention levels into two different arterial segments. Thus, MR-TMD-DCBs can be used to accurately deliver drug into multiple arterial segments with the use of a single DCB. The clinical outcomes of these findings need further investigation. Future long-term pharmacokinetics and safety studies will be performed to evaluate the safety and efficacy of the MR-TMD-DCB.