Ab. Fontaine et al., Evaluation of local abciximab delivery from the surface of a polymer-coated covered stent: In vivo canine studies, J VAS INT R, 12(4), 2001, pp. 487-492
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 endothelializatio
n of a polymer-coated, silicone-covered stent in a canine model.
MATERIALS AND METHODS: Six polymer-coated, silicone-lined Wallstents were s
oaked in 2 mg/mL of concentrated solution of I131-labeled abciximab for a p
eriod as long as 48 hours. Quantification of abciximab absorption was deter
mined by photon emission. Six maximally drug-loaded devices were then washe
d continuously with normal saline with use of a pustule pump apparatus. The
quantity of residual abciximab was determined by photon emission for a per
iod as long as 16 days. Eight similar devices las described previously) wer
e then implanted within the iliac arteries of four adult canines. Devices w
ere identical except that four of eight were maximally loaded with abcixima
b. For each animal, one control implant was placed in the right iliac arter
y and one experimental implant (drug loaded) was placed in the left iliac a
rtery, via right carotid cutdown. Animals were allowed to recover and no ch
ronic medications were given. After an interval of 6 weeks, the animals wer
e 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 neoint
ima 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 mug +/- 2.99 per device. De
vices were fully saturated at 24 hours. Forty percent was absorbed at 1 hou
r, and 60% and 80% were absorbed at 4 hours and 12 hours, respectively. Reg
arding elution, 30% of abciximab was washed out after 1 hour. There was a g
radual elution of the drug to 16 days, with approximately 40% remaining at
the end of the term. Mean neointimal thickness was 995 mum +/- 597 for the
experimental group and 1,738 mum +/- 1,042 for the control group. The diffe
rence was significant (P <.05).
CONCLUSIONS: Absorption and elution of abciximab from the surface of a cove
red stent is feasible. Local delivery of abciximab from the surface of this
covered stent reduced the thickness of endothelial lining in the canine il
iac artery compared to control.