Abstract
OBJECTIVE: Drug coated balloons (DCBs) are used to treat peripheral artery disease (PAD) but concerns about their efficacy and safety persist. Current evaluation methods, relying on benchtop studies and animal models, do not replicate the complexity of human PAD lesions. This study aimed to develop a novel methodology to assess paclitaxel delivery from DCBs to human peripheral arteries with complex plaque morphologies using scanning electron microscopy (SEM) with the purpose of examining how plaque morphology and vessel preparation affect drug transfer in human cadaveric legs. METHODS: An amputated leg model from patients with PAD and standardised vessel preparation, imaging, and quantification methods was used. Arteries were treated with plain balloon angioplasty, cutting balloon angioplasty, or no preparation before DCB treatment. Vessels were imaged with high vacuum SEM, and drug coverage was quantified with ImageJ. Lesions were classified as nodular or smooth based on magnetic resonance imaging. Drug distribution was analysed at 300×300 μm field of view (FOV), categorised as minimal, moderate, good, or excellent. RESULTS: SEM was effective at imaging paclitaxel crystals transferred to the vessel wall. Plaque morphology affected the amount of drug transferred with smooth plaques exhibiting greater drug coverage than nodular plaques. In nodular plaques, drug was concentrated on the protruding portions of the plaque and not in the recesses, while smooth plaques showed more uniform distribution. Excellent coverage was seen in 38.31% of FOVs of smooth plaques vs. 10.58% of nodular plaques. Drug transfer was more consistent in smooth vessels, regardless of vessel preparation method. Cutting balloons enhanced drug delivery when grooves were formed. CONCLUSION: This SEM based method effectively evaluated drug transfer in human PAD lesions, revealing greater drug delivery in smooth lesions and the impact of vessel preparation. This novel analytic model offers a platform for optimising DCB strategies to improve PAD patient outcomes.