The long range goal of this research program is to test several devices, based on the well-established basic principle of electroporation which allows delivery of exogenous molecules, intracellularly or pericellularly, and achieve effective and sustained delivery of various antithrombotic/antiproliferative agents into arterial wall. Application of this technology may overcome problems associated with the existing modality of drug delivery- systemic or local. Major application of such delivery would be in the areas of restenosis and treatment of intravascular thrombus. The Phase I proposal will deal with the following specific aims (i) extend the preliminary results obtained with the double-balloon electroporation catheter to include both the norma balloon-injured artery and the atherosclerotic rabbit models, serially, up to one month, with morphometric measurements, e.g., intima to media ratio, (ii) quantitate amount of heparin uptake by the mouse monoclonal anti-FITC probe that would bind to the FITC-labeled heparin, (iii) determine blood coagulation parameters, particularly APTT, for the pulsed and non-pulsed arteries, (iv) fabricate a prototype perfusion chamber and carry out in vitro studies with excised arteries or aorta and optimize pulsed parameters for maximum uptake of the agent, (v) obtain electric field plots using a software package for a given configuration of the catheter.
The technique will allow development of devices for sustained, effective and in vivo local delivery of heparin and similar drugs which may overcome problems associated with the current mode of delivery.
