Sustained local delivery of heparin to the rabbit arterial wall with an electroporation catheter.
Current methods of local drug delivery frequently fail to achieve a prolonged therapeutically effective tissue drug level without producing vascular trauma. A novel double-balloon catheter system, incorporating electroporation technology, has been designed and tested to deliver heparin into rabbit carotid arteries in an overstretch balloon injury model in vivo. Following arterial injury, fluoresceinated heparin was delivered into the volume between the two inflated balloons, and the artery was subjected to an electrical pulse. Catheter deployment and endovascular electrical pulsing were well-tolerated in all animals (N = 21) without adverse hemodynamic and histological changes. Periodic arterial blood samples revealed no abnormalities in the clotting profile or any gross morphological changes in the blood cells up to 8 hr after treatment. Much stronger heparin fluorescence was detected throughout the vessel layers for at least 12 hr in the pulsed samples compared to the control. Histochemical staining of the tissue showed intracellular localization of heparin. Endovascular electroporation may provide better retention and higher therapeutic efficacy than can be achieved by conventional systemic delivery of heparin at clinically safe concentrations.
Dev
N B
NB
Division of Pediatric Cardiology, Case Western Reserve University, Cleveland, Ohio, USA. nbdev@genetronics.com
Preminger
T J
TJ
Hofmann
G A
GA
Dev
S B
SB
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001794:Blood Pressure; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002406:Catheterization, Peripheral / Q000295:instrumentation*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation*; D018274:Electroporation; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007269:Injections, Intra-Arterial; D008297:Male; D011817:Rabbits; D012449:Safety; D016896:Treatment Outcome
D000925:Anticoagulants; D006493:Heparin