Related Experiment Videos
Boundary layer drug delivery using a helical catheter
C P Markou1, J E Brown, M D Pursley
1Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA.
Insights
A novel helical catheter delivers drugs locally to blood vessel walls, significantly reducing clot formation. This targeted approach enhances antithrombotic and antiproliferative agent efficiency, potentially lowering therapy costs.
Area of Science:
- Biomedical Engineering
- Vascular Medicine
- Drug Delivery Systems
Background:
- A new catheter-based system for localized endovascular drug delivery has been developed.
- The helical catheter is designed for percutaneous deployment, with its helical tip placed near the target vascular site for direct contact with the vessel wall.
- This method aims for efficient delivery of antithrombotic and antiproliferative agents to prevent vascular occlusion, heart attacks, and strokes.
Purpose of the Study:
- To evaluate the efficacy of a novel helical catheter for local endovascular drug delivery.
- To demonstrate the catheter's ability to retain infused drugs in the vessel wall boundary layer.
- To assess the antithrombotic potential of the helical catheter in a preclinical model.
Main Methods:
- In vitro evaluation using optical dye density measurements of Evans blue dye under steady flow conditions.
- In vivo assessment of antithrombotic capacity in a baboon arteriovenous shunt model using a thrombogenic Dacron vascular graft.
- Administration of Integrelin (glycoprotein IIb/IIIa inhibitor) and hirudin (antithrombin) via the helical catheter.
Main Results:
- Flow visualization confirmed high concentrations of infused dye retained near the vessel wall.
- Significant reductions in platelet deposition on the graft surface were observed: 82-97% with Integrelin and 68-92% with hirudin.
- Local antithrombotic effects were 200-fold (Integrelin) and 30-fold (hirudin) more efficient than systemic administration.
Conclusions:
- Local drug infusion via the helical catheter achieves high concentrations at target sites.
- This approach minimizes systemic drug exposure and potential side effects.
- The method offers potential cost savings through reduced drug requirements.
Background:
A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid 'boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes.
Methods:
The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow system under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate = 100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25-1.0 microg/min) and hirudin (an antithrombin; doses: 10-100 microg/min) were used to inhibit thrombus formation.
Results:
Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudin) over 1-2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than systemic administration of the same agents.
Conclusions:
Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid systemic effects, and can reduce cost of therapy by reducing total drug requirements.