title: Efficiency of drug delivery to the coronary arteries in swine is dependent on the route of administration: assessment of luminal, intimal, and adventitial coronary artery and venous delivery methods.
abstract: OBJECTIVE
  To compare the efficiency of five different drug delivery methods to the coronary artery in swine.
  
  
  METHODS
  A nanoparticle-albumin-bound, nonradioactive isotopic marker was administered within the left anterior descending coronary artery (LAD) through a microinfusion catheter (MIC: adventitial, n = 8, and luminal, n = 4), a porous drug infusion balloon (DIB: intimal, n = 4), and a straight catheter (SC: luminal, n = 2) and within the superior vena cava (SC: intravenous, luminal, n = 2). The distribution of the marker in heart, lung, liver, kidney, muscle, blood, urine, and bile was determined 68-84 minutes after delivery. The heart was sectioned into six axial slices and each slice divided into four quadrants. The marker content was assayed by neutron bombardment and the total counts of disintegrations per minute (DPM) expressed as a percentage of the control for each device delivery control.
  
  
  RESULTS
  After luminal delivery with the nonactuated MIC (MIC-NA) or intimal delivery with the DIB, 0.17% ± 0.07 and 0.39% ± 0.09, respectively, less than 0.39% of the total marker was detected in the heart. After adventitial delivery with the actuated MIC (MIC-A), 63.1% ± 9.9 of the total marker was detected in the heart. Marker was only detected in quadrants containing the coronary LAD, with the highest level in the middle slice and lower marker levels in consecutive proximal and distal heart slices. The nonactuated MIC-NA and DIB drug infusion balloon patterns of marker distribution were similar to those of actuated MIC-A, although with reduced levels. These delivery methods were also associated with considerably more marker detected in the lungs and liver: at least 22% compared with 1.34% ± 1.34 for the actuated MIC-A There was one delivery failure with the actuated MIC.
  
  
  CONCLUSIONS
  Catheter-based adventitial delivery with the MIC-A represents a more efficient delivery method for retention of vascular therapeutics.
authors.affiliation: Office of Science and Engineering Laboratories, US Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, Maryland, USA. john.karanian@fda.hhs.gov
authors.forename: John W
authors.initials: JW
authors.lastname: Karanian
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Peregoy
authors.forename: O Alberto
authors.initials: OA
authors.lastname: Chiesa
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Murray
authors.forename: Chul
authors.initials: C
authors.lastname: Ahn
authors.forename: William F
authors.initials: WF
authors.lastname: Pritchard
mesh_terms: D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D013552:Swine
chemical_list: D000418:Albumins