Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.
BACKGROUND
Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating.


RESULTS
For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining.


CONCLUSIONS
Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.
Voisard
Rainer
R
Department of Internal Medicine II-Cardiology, University of Ulm, Germany. rainer.voisard@medizine.uni-ulm.de
Stemberger
Axel
A
Baur
Regine
R
Herter
Tina
T
Hähnel
Iris
I
Resch
Ansgar
A
Seliger
Christian
C
Hemmer
Wolfgang
W
Hannekum
Andreas
A
Hombach
Vinzenz
V
Alt
Eckhard
E
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D001026:Coronary Artery Bypass; D023903:Coronary Restenosis / Q000517:prevention & control*; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage*; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D015607:Stents
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D016285:Iloprost; D017239:Paclitaxel