Boundary layer drug delivery using a helical catheter

• Published in: Journal of controlled release 1998-04, Vol.53 (1), p.281-288
• Main Authors: Markou, Christos P, Brown, Joe E, Pursley, Matt D, Hanson, Stephen R
• Format: Article
• Language: English
• Subjects: Animals; Arteriovenous Shunt, Surgical; Biological and medical sciences; Catheterization; Drug Delivery Systems; General pharmacology; Hirudins - pharmacology; Local drug delivery; Male; Medical sciences; Papio; Peptides - pharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - pharmacology; Thrombosis; Thrombosis - prevention & control
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(97)00262-9

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 μg/min) and hirudin (an antithrombin; doses: 10–100 μg/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.