Evaluation of local abciximab delivery from the surface of a polymer-coated covered stent: in vivo canine studies.

Autor: Fontaine AB; Department of Radiology, University of Washington Medical Center, 1959 NE Pacific St., RR-215, Seattle, WA 98195, USA., Borsa JJ, Dos Passos S, Hoffer EK, Bloch RD, Starr F, So C
Jazyk: angličtina
Zdroj: Journal of vascular and interventional radiology : JVIR [J Vasc Interv Radiol] 2001 Apr; Vol. 12 (4), pp. 487-92.
DOI: 10.1016/s1051-0443(07)61888-0
Abstrakt: Purpose: To determine the in vitro feasibility of abciximab absorption and elution from a polymer-coated, silicone-covered stent, and to determine the in vivo effect of local delivery of abciximab concerning endothelialization of a polymer-coated, silicone-covered stent in a canine model.
Materials and Methods: Six polymer-coated, silicone-lined Wallstents were soaked in 2 mg/mL of concentrated solution of I131-labeled abciximab for a period as long as 48 hours. Quantification of abciximab absorption was determined by photon emission. Six maximally drug-loaded devices were then washed continuously with normal saline with use of a pustule pump apparatus. The quantity of residual abciximab was determined by photon emission for a period as long as 16 days. Eight similar devices (as described previously) were then implanted within the iliac arteries of four adult canines. Devices were identical except that four of eight were maximally loaded with abciximab. For each animal, one control implant was placed in the right iliac artery and one experimental implant (drug loaded) was placed in the left iliac artery, via right carotid cutdown. Animals were allowed to recover and no chronic medications were given. After an interval of 6 weeks, the animals were killed. Implants were isolated and perfused with 10% buffered formalin at a pressure of approximately 100 mm Hg for a period of 1 hour. Each implant was encased in methacrylate, sectioned into six equal segments, ground and polished, and stained with hematoxylin and eosin. Each slide was projected on a screen and the thickness of the neointima quantified. The mean neointima was determined for control and experimental groups, and compared for a potential significant difference with a Student t test.
Results: Mean absorption of abciximab was 21.53 microg +/- 2.99 per device. Devices were fully saturated at 24 hours. Forty percent was absorbed at 1 hour, and 60% and 80% were absorbed at 4 hours and 12 hours, respectively. Regarding elution, 30% of abciximab was washed out after 1 hour. There was a gradual elution of the drug to 16 days, with approximately 40% remaining at the end of the term. Mean neointimal thickness was 995 microm +/- 597 for the experimental group and 1,738 microm +/- 1,042 for the control group. The difference was significant (P <.05).
Conclusions: Absorption and elution of abciximab from the surface of a covered stent is feasible. Local delivery of abciximab from the surface of this covered stent reduced the thickness of endothelial lining in the canine iliac artery compared to control.
Databáze: MEDLINE