Introduction: Advanced Catheter Therapies (ACT) has designed the Occlusion Perfusion catheter (OPC) to function as a universal agent-delivery system that will accommodate any therapeutic agent, including pharmaceuticals, biologics, and live cells.
Objectives: To demonstrate the ability of the OPC to deliver an agent circumferentially and longitudinally into the media of the vessel wall, overcoming the limitations of a drug-coated balloon and/or stent.
Methods: The OPC is a five-lumen catheter designed with proximal and distal occlusion balloons, a center space-occupying balloon, an inflow port, an outflow port, and a guidewire lumen compatible with a standard 0.014˝ wire. It is a 5 Fr catheter compatible with a 6 Fr sheath. A fiberoptic pressure sensor is incorporated into the inflow lumen to monitor treatment chamber pressure. Occlusion balloons define the treatment region. The proximal and distal occlusion balloons are inflated simultaneously to control blood flow and create a treatment chamber. In addition, they serve to prevent systemic distribution of the agent. The fourth and fifth lumens are for inflow and outflow ports located within the established treatment chamber. The trapped blood is removed from the treatment chamber by flushing with saline. The space-occupying balloon can be inflated to minimize the amount of therapeutic agent required when indicated. This balloon never touches the vessel wall. After the blood has been evacuated, the therapeutic agent is delivered. A sensor monitor controls and optimizes pressure within the chamber for penetration into the media of the vessel wall, longitudinally and circumferentially.
Results: Confocal analysis of the vessel wall demonstrated delivery of fluorescent paclitaxel within media and adventitia, circumferentially and longitudinally. PK analysis demonstrated a straight line of 0.1 µg/mL for 72 hours. According to Axel et al, the effective range of paclitaxel is 0.0085 to 0.85 µg/mL to effect a 90% to 99% inhibition of human arterial smooth muscle cells (SMCs). Seven-day scanning electron microscopy demonstrated that paclitaxel delayed the healing effect. Twenty-eight day histology demonstrated a normal endothelium. Live cell testing demonstrated that the OPC can deliver live cells with minimal mechanical damage at a wide range of pressures.
Conclusions: Preclinical testing conclusions: The OPC (1) delivers an agent circumferentially and longitudinally into the vessel wall; (2) delivers the effective range of paclitaxel for 90%-99% inhibition of human arterial SMCs, maintaining normal intimal endothelial function by non-coating; (3) delivers multiple agents; (4) supports multiple use in the same patient, above and below the knee; (5) offers controlled pressure within the chamber that negates the requirement for accurate balloon-to-wall measurements; (6) delivers live cells with minimal mechanical damage to the cell membrane; (7) negates blood-agent admixture; and (8) minimizes systemic effect via flushing.