Efficiency of drug delivery to the coronary arteries is dependent on the route of administration in swine: assessment of luminal, intimal, and adventitial intra-coronary and venous delivery modes with non-radioactive isotopic labels
John W. Karanian, PhD (1); Jennifer Peregoy (1); Alberto Chiesa, DVM, PhD (1); Chul Ahn, PhD (2); William F. Pritchard, MD, PhD (1)
(1) FDA, Center for Devices and Radiological Health, OSEL Laboratory of Cardiovascular and Interventional Therapeutics, Laurel, MD, USA
(2) FDA, Office of Surveillance and Biostatistics, Division of Biostatistics, Laurel, MD, USA
Abstract
Objective: Delivery of a nanoparticle-albumin-bound marker was compared in swine across 4 different intracoronary arterial methods and 1 central venous delivery method. Marker delivery through a micro-infusion catheter (MIC: intimal and adventitial method), guide catheter (GC; IA and IV: luminal methods) and porous PTCA infusion catheter (PIC: intimal method) was evaluated in order to define coronary delivery efficiency for each device.
Methods: In vivo marker levels and distribution in the heart, lung, liver, kidney, muscle, blood, urine and bile was determined following each intracoronary (LAD) and venous (SVC) delivery method. All tissue samples were excised 68-84 minutes following delivery. The heart was processed into six 1.5cm slices (S:1-6) and each slice was divided into four quadrants (Q:A-D). All tissue samples were dried and total counts (DPM) expressed as a percentage of each device control for each delivery method.
Results: Following intimal delivery with the non-actuated MIC (MIC-NA) and PIC less than 0.34% of the total marker was detected in the heart compared to 63% following adventitital delivery with the actuated MIC (MIC-A) . The marker was only detected in the left myocardium quadrant containing the LAD (Q:A) with no marker detected in the remaining left myocardial sections (Q:B-D), right myocardium or apex. The marker was detected in the LAD coronary quadrant (Q:A) of at least three consecutive slices (e.g., S:2-4) with the highest level in the middle coronary slice and lower marker levels in the proximal and distal coronary slices. No marker was detected in the coronary or myocardial sections following GC-IA or GC-IV deliveries. In contrast to the MIC-A, the MIC-NA, PIC, GC-IA and GC-IV delivery methods were associated with considerably more marker detected in the lungs and liver: 1.3% for the MIC-A in comparison to at least 20% for all other delivery methods. The pattern of marker distribution in the coronary was bell-shaped and similar across delivery methods.
Conclusions: Catheter-based adventitial delivery (MIC-A) compared to intimal (MIC-NA, PIC) and luminal delivery (GC) represents a markedly more efficient delivery method for retention of vascular therapeutics.
Cardiovasc Revasc Med 2009;10(4):261-2. © 2009 Published by Elsevier Inc.
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