BOUNDARY-LAYER DRUG-DELIVERY USING A HELICAL CATHETER

Background: A catheter-based approach for local endovascular drug deli very has been developed. The catheter is deployed percutaneously, whil e the end of the catheter is in the form of a helix that is placed jus t proximal to the vascular site to be treated. The helices are in cont act with the vessel wall. A number of small holes is drilled in the co ils 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 admi nistration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. M ethods: 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 wa s inserted into a femoral arteriovenous shunt (blood flow rate=100 ml/ min) and placed proximal to a segment of highly thrombogenic Dacron va scular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glyco protein IIb/IIIa; doses: 0.25-1.0 mu g/min) and hirudin (an antithromb in; doses: 10-100 mu g/min) were used to inhibit thrombus formation. R esults: Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the v essel wall. In the animal experiments, platelet deposition on the Dacr on graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudi n) over 1-2 h of blood exposure. The local antithrombotic effects prod uced were found to be 200-fold and 30-fold more efficient than systemi c administration of the same agents. Conclusions: Local drug infusion using the helical catheter approach can achieve high drug concentratio n levels at target sites, may avoid systemic effects, and can reduce c ost of therapy by reducing total drug requirements. (C) 1998 Elsevier Science B.V.